Datasets:

9rofe

/

pubmed_reading_levels

like 0

Left ventricular thrombus in a 2-year-old boy with cardiomyopathy: lysis with recombinant tissue-type plasminogen activator. A 2-year-old boy with cardiomyopathy and clinical signs of cardiac failure presented with an echodense structure in the left ventricle. This structure was seen from different echocardiographic views adjacent to a hypokinetic area of the apex and lateral free wall. It was different in texture and motion from the underlying myocardium and thus met the diagnostic criteria of a left ventricular thrombus. This thrombus protruded into the cavum and was partly mobile. In view of a high embolic risk, thrombolytic therapy with recombinant tissue plasminogen activator was started. The thrombus resolved within 72 h without any embolic or bleeding complications. No recurrence of the thrombus was observed during a 3-month follow up period.

Multicenter clinical trials of fetal pH monitoring in the U.S.A. A multicenter collaborative study of the safety and clinical efficacy of the ROCHE fetal pH monitor has been started. A common protocol and reporting forms are used. As of April, 1978, 115 case reports have been received describing results with the latest hardware. The tissue pH monitor can be relied upon to monitor pH if the values are in the normal range. Comparison of tissue pH (tpH) with 146 capillary pH samples revealed 98% accuracy of tpH in classifying normal (greater than or equal to 7.20), but false tpH acidosis occurred in 6% of normals. Therefore, acidotic tpH values must be verified. Although six infants had some degree of trauma (small lacerations), there were no serious or permanent injuries.

Histopathologic sequence of events in adult mice undergoing lethal graft-versus-host reaction developed across H-2 and/or non-H-2 histocompatibility barriers. The sequence of histologic events in graft-versus-host reaction (GVHR) caused by major and/or minor histoincompatibilities was studied. It was discovered that GVHR may manifest itself in the form of two distinct multiphasic disease entities, depending on whether the donor cells are incompatible with the host for both major and minor histocompatibility antigens ("major GVHR") or for minor histocompatibility antigens alone ("minor GVHR"). The acute or major GVHR has four phases: 1) a transient phase of aplasia, 2) a repopulation phase, 3) a proliferative phase involving lymphoid, presumably immunocompetent, cells, and 4) a phase of acute organ rejection (terminal). The chronic or minor GVHR is characterized by six phases, namely: 1) a transient phase of aplasia, 2) a repopulation phase, 3) a phase of proliferation and tissue infiltration by lymphoid, presumably immunocompetent cells, 4) a phase of major immunologic injuries, 5) a phase of repair, and 6)a terminal phase with advanced sclerosis and proliferative glomerulonephritis. In acute or major GVHR the disease was manifested by the tissue reactions characteristic of acute organ rejection. Lesions were seen in the kidney, liver, bone marrow, lymph nodes, spleen, thymus, intestine, and skin. In the chronic or minor GVHR, tissue injuries were more widespread, affecting the collagen, vessel walls, adipose tissue, renal glomeruli, heart muscle, fascias of skeletal muscles, lymph nodes, spleen, thymus, bone marrow, intestine, skin, esophageal mucosa, and urinary tract. A pronounced plasma cell proliferation was a striking feature in the minor GVHR. Its evolution coincided with advanced thymic epithelial atrophy. It is suggested that the destruction of thymic epithelium resulted in depletion of suppressor T cells and, consequently, in an unopposed proliferation of plasma cells.

Permeability of muscle spindle capillaries and capsule. The permeability of capillaries in rabbit muscle spindles, intramuscular nerves, and extrafusal muscle to intraaortically infused horseradish peroxidase (HRP) was studied. The permeability of the capsule cells of the muscle spindles was also examined. Immediately following the infusion of HRP, most extrafusal capillaries contained a dense accumulation of HRP reaction product, which began to escape into the surrounding extracellular space within 2-3 min. In contrast, the concentration of HRP in the intrafusal and endoneurial capillaries was much lower than that in extrafusal capillaries, and HRP was never found outside the former vessels. In addition, HRP never completely penetrated through the spindle capsule from the extracellular into the periaxial space, although it was regularly found between the outer two or three layers of capsule cells. The results indicate that the permeability characteristics of the muscle spindle capillaries and capsule to the tracer protein HRP are very similar to those of capillaries in peripheral nerve.

The International Classification of Health Problems for Primary Care. Health problems of patients seen in the ambulatory setting are different from those encountered in the hospital, and the particular classification of diseases used should reflect these differences. The International Classification of Health Problems in Primary Care (ICHPPC) was designed for use by primary care physicians. It was tested in multiple sites in several countries for one year and has been approved by the World Organization of National Colleges and Academies of Family Medicine-General Practice and other groups concerned with the classification of diseases. The ICHPPC permits classification of the most important part of an ambulatory data see. Data generated by using this classification facilitate outreach to a practice population, construction of diagnostic profiles of health care providers, design of curriculum and health services research.

[Thrombotic reactions of vascular anastomoses: comparison of model studies with experimental findings]. The areas of predilection for atherosclerosis and thrombosis in the vascular system are characterized by curvature, branching, bifurcation or embankment. We have investigated induced thrombus formation at arteriolar bifurcations with migrating stagnation points and local vortex flow. Thrombogenic endothelial lesions were produced in rat mesenteric arterioles by argon laser injury or by photochemical reactions (using FITC-dextran 70). The following items have been evaluated: local red blood cell velocity, geometry of the vessel, localization of the first thrombus growth. The first appearance of thrombus formation at presumably (re-) attachment points at bifurcations in the microcirculation could be directly demonstrated by intravital microscopy.

[Circulatory dynamics in the conjunctival vessels in ischemic heart disease with and without hypertension]. The circulatory dynamics was studied in the conjunctival vessels of 45 patients with ischaemic heart disease without hypertension (12 patients with myocardial infarction including) and in 24 patients with ischaemic heart disease and hypertension. The method of biomicroscopy of the conjunctiva permits to examine the shape of the microvessels, the vascular background and the density of the pattern, as well as the nature of the blood flow. The patients with ischaemic heart disease without hypertension had more distinct changes, in some cases -- with irreversible discontinuity of the flow (aggregation of the erythrocytes in myocardial infarction). In ischaemic heart disease with hypertension the flow in the venules restores completely by the end of therapy. Reversible changes in the microcirculation were demonstrated in cases of a good effect of therapy, as well as the possibilities of timely diagnosis of complications in repeated examinations of the conjunctival vessels.

[Sports accidents of tennis players (author's transl)]. An analysis of 144 sports accidents of 275 tennis players in Switzerland (203 men, 72 women) showed fractures of bones in 5,5% open wounds in 14,5%, torsions in 33% and other injuries in 47%. The head was injured in 9,5 and the legs in 76%, the arms in 11,5% and the trunk in 11,5%. Two fifth of all leg injuries were on the left side, three fifth on the right side. The arms were hurt in 98% on the right and only in 2% on the left side. Causes of accidents were in 21% slipping on wet ground, in 17% related to the rackets, in 33% a too speedy start with damage to muscles and tendons, in 14% stepping on tennisballs lying on the ground. A tennis sport accident required an average of 35,8 days of treatment by a medical doctor and an average of 0,7 days of clinical treatment. Already 33% of the men and 26% of the women suffered from the so called "tennis-elbow".

Production of high-titer helper virus-free retroviral vectors by cocultivation of packaging cells with different host ranges. The titer of retroviral vectors can be increased by cocultivation of retrovirus packaging cells that produce a vector with packaging cells having a different host range. Multiple rounds of infection occur in such cultures, producing an amplification of vector copy number and titer. Production of a vector with a very high titer of over 10(10) CFU per ml of conditioned medium has been reported, although replication-competent helper virus was also present. Since helper-free virus is a requirement for many applications of retroviral vectors, we repeated this procedure with a modified vector and achieved a 2- to 10-fold amplification of vector titer in the absence of helper virus, up to 2 x 10(7) CFU/ml. We have also repeated these experiments with the same vector and methods described previously or have assayed virus from the high-titer vector-producing cell line reported previously and observed maximum titers of 10(8) CFU/ml, invariably accompanied by helper virus. Thus, while amplification of vector titer in the absence of helper virus is possible, some unexplained difference in the assays for virus titer must account for our inability to obtain the exceptionally high vector titers that were reported previously.

Enhancement of immunoreactivity of von Willebrand factor in vascular endothelial cells of rat organs after glucocorticoid administration. Our study showed that synthetic glucocorticoids are potent mediators of vWF-reactivity in rat fetal placental, liver and lung vascular elements. However, it is not yet possible to draw final conclusions from these results obtained only by immunohistochemical studies using antibody against vWF, since the mechanisms in factor VIII/vWF are highly complex. Further investigations for example with anti-vW AgII and measurements of blood vWF levels after treatment with synthetic glucocorticoids may deliver more insight into the mechanisms of action of these drugs. Investigations after treatment of pregnant rats with methylprednisolone might help, in addition, to find out whether the increased vWF-reactivity in caused by special substituents in the steran ring of the glucocorticoids.

Role of polyamines in gastrointestinal mucosal growth. The polyamines have been under active investigation for nearly three decades. There is a great deal of evidence that they play an important role in gastrointestinal mucosal growth, but the mechanisms through which this role is carried out are still not fully explained. This review examines the role of the polyamines in the regulation of mucosal growth, the control of intracellular polyamine levels, the biosynthesis of the polyamines, and some known mechanisms of their action. Finally, we propose a model of polyamine action that reconciles the effects of various trophic agents and situations in which growth is stimulated along with concomitant changes in polyamine levels. It accounts for both humoral and gradient-oriented features of various adaptive responses of the gastrointestinal mucosa and is intended to provide a framework for the future investigation of the role of the polyamines in this tissue.

Studies in owl monkeys leading to the development of a synthetic vaccine against the asexual blood stages of Plasmodium falciparum. During the development of a synthetic vaccine for human use against the asexual blood stages of Plasmodium falciparum, monkey trials were performed to assess safety, immunogenicity, and protectivity. We determined the minimal infective dose of the P. falciparum FVO strain, the kinetics of the immune response induced by vaccination with the synthetic peptide mixture (S7 + S12 + S17) or the synthetic hybrid polymeric protein SPf66, and the induction of protective immunity against the experimental challenge with 2 P. falciparum strains. A clear boosting effect was observed, determined by the increased antibody titers against synthetic peptides S7, S12, S17, and SPf66, and by improvement in the protective immune response against the challenge. These studies suggest that either the peptide mixture or the synthetic hybrid polymeric protein are excellent choices for the development of a vaccine against P. falciparum.

Situational factors associated with AIDS risk behavior lapses and coping strategies used by gay men who successfully avoid lapses. While most gay men have reduced behavior practices at high risk for HIV infection, there is growing evidence that many also lapse to unsafe sex. This study examined situational factors related to risk behavior lapses as well as coping strategies used by men who successfully resist lapse urges. A convenience sample of 470 men patronizing gay bars or attending social organization meetings in four cities was surveyed. Forty-five percent of men were classified as "lapsers" (those who had had unprotected anal intercourse in the previous 6 months) and 24% were classified as "resisters" (those who successfully resisted urges to engage in this behavior). All provided information concerning the importance of factors related to the most recent occurrence of either unsafe sex or resisting unsafe urges. Most episodes of unsafe sex occurred outside monogamous relationships and with partners of unknown HIV serostatus, although simply inquiring about partner serostatus was relatively common. Lapsers rated affectionate feelings and wishing to please a partner as well as spontaneity of unsafe sex as the most important situational factors surrounding high-risk behavior. Resisters of unsafe sex urges reported active cognitive self-guidance, experience in safe sex, and recall of both AIDS fears and safety benefits as their most important coping strategies. Gay men who continue high-risk behavior may be overrelying on partner reports of negative serostatus. Lapse prevention approaches tailored to situations that create increased risk vulnerability must be developed. Teaching skills already used by men who successfully resist unsafe sex urges might be one approach.

The management and outcome of late post-infarct ventricular tachycardia presenting to a district general hospital. A review was undertaken of late post-infarct ventricular tachycardia in a district hospital cardiac care unit in order to study the clinical course of a total population of such patients from initial presentation to ultimate outcome. Thirty-six patients with this diagnosis were identified over a 3 1/2-yr period. Twelve were treated by empirically chosen antiarrhythmic drugs. Twenty-four were referred for electrophysiologically guided treatment, of whom 16 were treated by antiarrhythmic drugs, 3 by anti-ischaemic measures alone, and 5 by non-pharmacological antiarrhythmic treatments (antiarrhythmic surgery, percutaneous ablation, defibrillator implantation, cardiac transplantation). Of those treated empirically, 4 died in hospital of their arrhythmia, 1 died suddenly at home, and 2 suffered non-fatal arrhythmia recurrences during mean follow-up of 20 months. There were no arrhythmic deaths in those whose treatment was guided by serial electrophysiology studies, although 4 patients died of cardiac failure or reinfarction, and 3 were hospitalised with a recurrence of ventricular tachycardia during mean follow-up of 16 months. Age, concomitant medical problems and the apparent response to initial antiarrhythmic therapy were the main factors influencing management decisions. The apparent superiority of more intensive management strategies based on electrophysiology studies must be interpreted in the context of the selection processes applied to the total population initially presenting.

Purification of recombinant human growth hormone by isoelectric focusing in a multicompartment electrolyzer with Immobiline membranes. Recombinant human growth hormone (r-hGH) expressed in Escherichia coli, was 70-80% purified by a combination of ion-exchange chromatography and metal ion affinity chromatography. For the last purification step, a multicompartment electrolyzer was used, containing three compartments delimited by isoelectric membranes and two additional anodic and cathodic chambers. The central compartment was situated between two membranes having isoelectric points (pI) of 5.08 (anodic) and of 5.16 (cathodic), i.e. equidistant from the pI value of hGH (pI 5.12). r-hGH was isoelectric between these two membranes and could not leave the central chamber, while more acidic and more cathodic impurities collected in the two lateral chambers under the influence of the electric field. The r-hGH, thus purified, exhibited a single band by isoelectric focusing (IEF) in immobilized pH gradients (IPG) and gave recoveries greater than 90%. The problem of isoelectric precipitation in a practically ion-free environment was alleviated by focusing in 30% glycerol added with 1% neutral detergent (Nonidet-P40). The latter was eliminated by passage through a Q-Sepharose column after collecting the pI 5.12 band from the electrolyzer. Also the pre-hormone (pre-hGH) can be purified in a similar manner (30% glycerol, 1% Nonidet P-40) between two membranes having pIs 4.77 (anodic) and 4.87 (cathodic) (pre-hGH pI 4.82). This paper demonstrates the possibility of purifying by a focusing process also poorly soluble proteins at the pI.

The effect of inhibition of prostaglandin synthesis on plasma renin activity and blood pressure in essential hypertension. The influence of oral indomethacin treatment (75 mg daily for a week) on urinary excretion of prostaglandin (PG) F2alpha, plasma renin activity (PRA), blood pressure (BP) and electrolyte excretion (Na+ and K+) was studied in 21 patients with untreated essential hypertension (9 women and 12 men, aged from 40 to 45 years). PGF2alpha excretion and PRA were markedly suppressed by indomethacin in both sexes. A close correlation was found between the decreases in PGF2alpha excretion and PRA. 13,14dihydro-15keto-PGF2alpha (a metabolite of PGF2alpha) excretion also tended to be lowered during the indomethacin treatment. BP tended to increase but urine volume and electrolyte excretion were unchanged during the indomethacin period. The results suggest that in essential hypertension inhibition of the PG synthesis causes a concomitant suppression in PRA and may slightly increase BP.

[Surgical revascularization in acute myocardial infarct]. To determine the potential role of emergency surgical revascularization as treatment of acute myocardial infarction (AMI), results in 79 patients undergoing operation for myocardial revascularization during AMI from January 1986 to January 1991 were reviewed. Clinical characteristics for inclusion in the study were: 1) emergency operation; 2) persistent angina not controlled by medical therapy; 3) fixed ST segment elevation until surgical procedure, independently from magnitude of enzymatic levels. The 79 patients were divided in 2 groups: 27 with AMI or evolving AMI (Group 1); 52 with AMI due to complications during PTCA (Group 2). Twenty-eight patients had extremely severe clinical conditions. Mean interval between the beginning of AMI and operation was 4.2 +/- 6.7 hours, with a statistically significant difference between Group 1 (8.7 +/- 10.0) and Group 2 (1.9 +/- 1.0). One hundred ninety-two grafts were performed (2.4 +/- 1.1 grafts/patient). Overall hospital mortality was 10.1% (CL 6.7-13.3) (8 deaths) with a difference between Group 1 [18.5% (CL 10.7-25.3)] and Group 2 [5.8% (CL 4.7-6.6)] (p = 0.074). The incidence of perioperative myocardial infarction was 30.4% (CL 24.9-35.1) for that one in the area of ischemic muscle and 2.6% (CL 0.8-4.1) for infarction in remote muscle. Multivariate analysis for the entire series (79 patients) identified as independent predictors of increased in-hospital mortality: preoperative cardiogenic shock (p = 1.000E-4) and hyperlipidemia (p = 0.008). In Group 1 multivariate analysis identified as independent predictors of increased in-hospital mortality: the attempt of revascularization by PTCA and hyperlipidemia; in Group 2: preoperative need of mechanical ventilatory support.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hereditary angioedema, a rare cause of recurrent abdominal pains. A report of 2 clinical cases and comments of a general nature]. Two clinical cases of recurrent abdominal pain are reported. These led to the unusual diagnosis of hereditary angioedema due to deficiency of C1 esterase inhibitor (C1-INH). The difficulties of identifying this genetic disease were caused by the variability of its clinical expression: the alteration of an autosomal dominant gene triggers angioedema attacks that may strike the cutaneous, gastroenteric and respiratory apparatus with differing intensity. Various subjects suffering from hereditary angioedema were found in the genealogical trees of the two patients, but all had extraintestinal symptoms of very variable intensity. Measurement of C4 and C1-INH made it is possible to identify in the first family a functional defect of C1 esterase inhibitor and in the second a quantitative defect in the same inhibitor.

Functional studies on human peritoneal eosinophils. A number of functional studies were performed on essentially pure eosinophil preparations obtained from the ascitic fluid of a patient with eosinophilic gastroenteritis. These cells responded to chemotactic factors including a bacterial factor, partially purified C5a, and factors generated from serum or ascitic fluid. The chemotactic activity generated in the patient's ascitic fluid was capable of attracting both neutrophils and eosinophils, was dependent on the presence of complement components, and was identified as C5a. Metabolic studies demonstrated that particle ingestion by eosinophils was associated with a marked increase in hexose monophosphate shunt activity ([1-14C]glucose oxidation), H2O2 formation ([14C]formate oxidation), superoxide anion generation, chemiluminescence, thyroid hormone degradation, iodination, and estrogen binding. This postphagocytic metabolic burst by eosinophils was qualitatively similar to that observed in neutrophils, but for several parameters the eosinophil response was greater than the neutrophil response.

Thematic analysis in agrammatic comprehension: syntactic structures and task demands. Aphasics' ability to assign thematic roles during sentence comprehension was investigated. The study was motivated by the hypothesis that capacity limitations, e.g., due to slowed processing operations, interact systematically with certain aspects of structural analysis more than with others. Experiments using a sentence-picture matching paradigm were conducted with several agrammatic Broca's and paragrammatic Wernicke's patients. Experiment 1 tested comprehension of various syntatic structures. The astoundingly good performance in Experiment 1 for both patient groups was attributed to the low task demands of the experiment. Raising the task demands, by delaying presentation of the relevant picture set in Experiment 2, resulted in a significant decrement of comprehension performance for agrammatic Broca's aphasics, but not for Wernicke's aphasics. Putting the main verb in the sentence-final position, as in Experiment 3, affected Wernicke's aphasics', but not Broca's aphasics' performance. In principle, one explanation for the performance differences between Experiments 1 and 2 for Broca's patient might be a deficit in these patients' verbal memory capacity. Therefore, verbal memory span on different word categories was tested in an additional experiment. No difference, however, was found between the Broca's patients' and the Wernicke's patients' capacity for verbal memory despite their different sentence comprehension profiles. The present data are taken to support the view that Broca's aphasics' comprehension behavior is due to the processing demands imposed by structural inference chains and not to a general reduction in verbal memory.

Effect of chronic ethanol feeding on factors leading to inappropriate intrapancreatic activation of zymogens in the rat pancreas. In rats fed control and ethanol-containing Lieber-DeCarli diets for a period of 12 months, the bile did not contain any enterokinase, the pancreatic juice did not contain any plasmin or thrombin, but in animals fed high fat diet with ethanol, trypsinogen and chymotrypsinogen were significantly increased and trypsin inhibitor decreased. In the tissue, free trypsin and cathepsin B were increased. Composite profile of trypsinogen in gel segments obtained from the pancreatic juice and the tissue showed higher peaks of cationic and anionic variants of trypsinogen in animals fed ethanol. There was no evidence of mesotrypsinogen or of enzyme Y in the juice or the tissue. These studies show that serine proteases and cathepsin B may play a major role in the pathobiology of alcoholic pancreatitis.

Oxygen consumption by rat lung after in vivo hyperoxia. We studied the influence of 48 and 96 hours of in vivo hyperoxia (O2 greater than 98 per cent) on O2 consumption by rat lung slices. After 48 hours of hyperoxia, lung O2 consumption expressed per mg of deoxyribonucleic acid or per left lung decreased to approximately 70 per cent of that of lungs from rats exposed to compressed air. After 96 hours of hyperoxia, there was no difference in lung O2 consumption per mg of deoxyribonucleic acid between rats exposed to O2 and those exposed to air, but lung O2 consumption per left lung was higher in rats exposed to O2 than in those exposed to compressed air. Lung ribonucleic acid content and the ratio of ribonucleic acid to deoxyribonucleic acid were significantly increased after 96 hours of hyperoxia. We concluded that the rate of lung metabolism is altered after in vivo exposure to high PO2.

Genes for the hook-basal body proteins of the flagellar apparatus in Escherichia coli. Of the more than 30 genes required for flagellar function, 6 are located between pyrC and ptsG on the Escherichia coli genetic man. This cluster of genes is called flagellar region I. Four-point transductional crosses were used to establish the position and order of the region I flagellar genes with respect to the outside markers ptsG and pyrC. Bacteriophage lambda-E. coli hybrids that contained most of the genes necessary for flagellar formation were constructed. The properties of specific hybrids that carried the region I fla genes were examined by genetic complementation and by measuring the capacity of the hybrids to direct the synthesis of specific polypeptides. The results of these tests with lambda hybrids and with a series of deletion mutations derived from the lambda hybrids demonstrated the existence of at least six flagellar-specific cistrons. These directed the synthesis of polypeptides with the following apparent molecular weights: flaV, 11,000; flaK, 42,000; flaL, 30,000 and 27,000; flaM, 38,000; flS, 60,000; and flaT, 35,000. Plasmid ColE1-E. coli hybrids with region I flagellar genes were also used to program the synthesis of polypeptides in minicell-producing strains. The polypeptides synthesized in these experiments were identical to polypeptides of the hook-basal body structure and helped to confirm the assignment of genes to specific polypeptides. The synthesis of all of these polypeptides was regulated by the same mechanism that regulates the synthesis of other flagellar-related structural components.

Autoradiographic analysis of second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults. Using [3H]inositol 1,4,5-triphosphate (IP3), [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]forskolin, we performed quantitative autoradiography to determine sequential alterations in second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults. Changes following three 2-min ischemic insults were compared with those following single 2- or 6-min ischemia. [3H]IP3 binding was extremely sensitive to ischemic insult, and more than 80% of the binding sites were lost after destruction of CA1 pyramidal cells following 6-min ischemia and three 2-min ischemic insults. Furthermore, a 30% reduction was observed after 2-min ischemia which leads to no neuronal loss. [3H]PDBu binding in the CA1 subfield decreased by 1 day after three 2-min ischemic insults and by 4 days after 6-min ischemia, and 40-50% reductions were observed at 1 month. In contrast, [3H]forskolin binding was relatively preserved. [3H]PDBu and [3H]forskolin binding transiently increased early in the reperfusion period. We also observed a difference in the pattern and severity of alterations between repeated ischemic insults and single ischemia.

Insulin and the phosphorylation of intracellular proteins. Protein phosphorylation is a ubiquitous form of posttranslational protein modification in mammalian cells which often serves to regulate protein function. Insulin alters the activity of a number of enzymes known to be regulated via phosphorylation. With the premise that altered protein phosphorylation might be an obligatory intermediate step in insulin action, we have examined the effects of insulin on the phosphorylation of the major phosphopeptides in adipocytes and hepatocytes. Insulin affects overall protein phosphorylation in two ways: 1) Insulin selectively stimulates the phosphorylation of a major peptide in adipose tissue (MW 123,000) and liver (MW 46,000) through a mechanism independent of cAMP and the cAMP-dependent protein kinase. Net dephosphorylation is not observed with insulin as the sole hormone. 2) Insulin antagonizes cAMP-directed protein phosphorylation. The mechanism of insulin-stimulated phosphorylation and the possible role of this phenomenon in overall insulin action is discussed.

Safety of therapy for allergic symptoms during pregnancy. We undertook a literature review to document whether certain therapeutic measures could be considered safe during pregnancy in the allergic patient. With the possible exception of brompheniramine, the commonly used antihistamine drugs appear to be safe during pregnancy. The bronchodilators ephedrine and theophylline also appear to be safe, as does cromolyn. Corticosteroids do not appear to have adverse effects in pregnancy beyond those well recognized in nonpregnant patients. Because side effects are reduced when steroids are administered as aerosols in the nose or lung, these preparations seem well suited for use in pregnancy. The safety of allergic immunotherapy has been confirmed. For asthma, annual influenza vaccination is indicated.

Treatment of psoriasis with a 311-nm UVB lamp. In a left-right comparative study, the Philips TL-01 sunlamp, a new UVB fluorescent lamp, was evaluated in 15 patients with symmetrical psoriasis. One half of the body was treated in a cabin containing TL-01 lamps, and the other half in a cabin containing TL-12 lamps. The patients were treated three times/week, and the study was conducted in a randomized, double-blind fashion. The percentage response of psoriatic lesions was determined on the tenth and twentieth exposures. The therapeutic effect of the TL-01 lamps was superior to that of the TL-12 lamps, and treatment was better tolerated, particularly with regard to episodes of burning. This new lamp appears to provide more effective and safer phototherapy for psoriasis.

Periosteal graft in scleromalacia. A case of scleromalacia perforans in a 60-year-old white male without any associated systemic diseases is reported. The patient had central retinal artery occlusion and Mooren's type of peripheral corneal degeneration in this eye preceding the development of scleromalacia. Various modalities of treatment, both medical and surgical, have been described in the literature and among surgical procedures various tissues were used as graft material in the areas of scleral thinning. We chose periosteum as the graft material on the basis of our experience with it in cases of "through-and-through" keratoprosthesis and the result has been very encouraging. Though our experience is limited to only one case, we feel that periosteum as graft material has a place in cases of scleromalacia.

Repair of transcriptionally active and inactive genes during S and G2 phases of the cell cycle. To study the effect of ultraviolet irradiation on S and G2 phases of the cell cycle, BB88 mouse cells synchronized by a double thymidine block were exposed to ultraviolet light, and rates of DNA synthesis and mitotic indexes were determined at regular intervals. It was found that with increasing ultraviolet dose, semiconservative DNA synthesis decreased and the sharp mitotic wave observed in the unirradiated cells gradually degenerated. To study repair, semiconservative DNA replication was inhibited with hydroxyurea at different time intervals after releasing cells from the block and the DNA synthesized as a result of repair of the ultraviolet damage was labeled with 5'-bromodeoxyuridine (BrdU). The newly repaired DNA was separated from bulk DNA by immunoprecipitation with monoclonal anti-BrdU antibody, labeled with 32P and hybridized to nine different gene and oncogene probes dot-blotted in excess on nylon membranes to determine their abundance in the repaired DNA. The results showed that: (a) the most actively repaired segment was a 211-bp sequence adjacent to the promotor region of the beta-actin gene; (b) all transcriptionally active genes were repaired at similar and constant rates throughout S and G2 phases; (c) the nontranscribed genes were repaired at much lower rates in early S phase, but later in S phase and especially in G2 phase, their repair rates increased and approached those of the transcribed genes.

[Human larva migrans visceralis infections with toxocara in the German Federal Republic. Serological investigations (author's transl)]. The microprecipitation test on second generation larvae of Toxocara canis has proved to be highly specific for the diagnosis of human larva migrans visceralis infection caused by Toxocara species. Out of a total of 2864 samples examined from 1969 to 1976, 248 were found to be positive. Besides a very frequently occurring eosinophilia eye affections, lung changes and involvement of the CNS are prominent clinical symptoms. The investigations show that larva migrans visceralis infections also occur in West Germany, even if more rarely than in other countries. The diagnosis is only seldom made because of the lack of uniformity of the clinical symptomatology.

Genetic modulation of RNA metabolism in Drosophila. III. Requirement for an rDNA-deficient X chromosome in YbbSuVar-3-mediated increases in RNA synthesis. Males of the genotype car bb/YbbSuVar-5 have an approximately two-fold increase in the rate of accumulation of 4S, 5S, 18S plus 28S and poly-A+ RNA molecules when compared to males of the genotype car bb/Ybb- (CLARK, STRAUSBAUGH AND KIEFER 1977; CLARK and KIEFER 1977). Experiments were designed to determine if the modulation of RNA metabolism by YbbSuVar-5 requires an rDNA deficiency on the X chromosome. Synthetic rates for 4S, 5S, and 18S plus 28S RNA's were measured in the genotypes Sam + iso/Ybb- and Sam + iso/YbbSuVar-5 by injecting adult males with 3H-uridine, allowing them to incorporate label for two hours, fractionating extracted RNA by polyacrylamide gel electrophoresis and determining the specific activities of RNA's (dpm/microgram RNA). The results of these determination showed that the synthetic rates for 4S, 5S, and 18S plus 28S RNA's are the same in these two genotypes, demonstrating that the YbbSuVar-5 chromosome does not increase transcription when paired with an X chromosome that is wild type for rDNA. Saturation hybridization was used to measure the rDNA content in several genotypes. These results showed that Sam + iso/YbbSuVar-5 males and Sam + iso/Ybb- males have equivalent amounts of rDNA.--These results are consistent with the suggestion that the Ybb- and YbbSuVar-5 chromosomes have similar amounts of rDNA. The nature of compensatory strategies in rDNA-deficient genotypes is discussed.

Effect of aurothiomalate on human mononuclear blood cells cultured in vitro. Human mononuclear phagocytes were exposed to aurothiomalate in various concentrations and at various stages in the differentiation from monocytes to macrophages in vitro. Monocytes exposed to aurothiomalate during the first 90 minutes of culture showed impaired engulfment capacity when tested 8 days after the exposure to the drug. It was found that aurothiomalate suppressed the digestion capacity in differentiated macrophages while the engulfment capacity was unaffected by the drug. During the period of differentiation from 90 minutes to 8 days of culture, exposure to aurothiomalate resulted in a dose dependent reduction in cell survival and differentiation. The effect of aurothiomalate on the blastoid transformation of lymphocytes following BCG stimulation was also tested. A strong and dose dependent inhibition of DNA synthesis was recorded. The inhibition of phagocytosis in mononuclear phagocytes and the inhibition of antigen-induced lymphocyte stimulation as demonstrated may help to explain the effect of aurothiomalate in patients suffering from rheumatoid arthritis.

Increase of IGF I binding to erythrocyte receptors during the TRH-test: correlation between IGF I binding and thyroid hormone values. The effects of TRH on insulin-like growth factor I receptors were investigated on erythrocytes from 7 GH-deficient children having plasma GH levels less than 10 ng/ml during two provocation tests. Intravenous injection of synthetic TRH (0.2 mg/m2) was followed by a marked increase of IGF I binding on erythrocytes, from 3.9% +/- 0.3% to 5.9% +/- 0.3% (P less than 0.005) after 1 hour and 7.3% +/- 0.4% (P less than 0.005) after 2 hours. The IGF I binding variations were due to an increase in both the receptor affinity and the number of sites. The levels of plasma GH, IGF I, T3, T4, free T4, TSH and prolactin having been determined during the TRH test at 0, 1 hour, and 2 hours after the injection, the increase in the IGF I binding to erythrocytes at the same time correlated with the rise of thyroid hormones: triiodothyronine T3 (P less than 0.001) and thyroxine T4 (P less than 0.005) and not with the level of the other hormones. These findings suggest that thyroid hormones play a role in the regulation of insulin-like growth factor I receptors.

Purification of mouse Ren 2 prorenin produced in Chinese hamster ovary cells. Renin is produced from a larger, inactive precursor, prorenin, by endoproteolytic removal of the amino-terminal prosegment. In this study, we have transfected Chinese hamster ovary cells with the expression plasmid of mouse Ren 2 preprorenin, and have purified mouse Ren 2 prorenin from the incubation medium of these cells by DEAE-Toyopearl chromatography, Blue-Toyopearl chromatography, and isoelectric focusing. Prorenin thus purified has a molecular mass of 42 kDa as determined by SDS-PAGE and an isoelectric point of 6.5. Amino-terminal sequencing has demonstrated that the purified prorenin has the amino-terminus predicted from the nucleotide sequence of mouse Ren 2 preprorenin cDNA.

Chemistry and toxicity of flame retardants for plastics. An overview of commercially used flame retardants is give. The most used flame retardants are illustrated and the seven major markets, which use 96% of all flame-retarded polymers, are described. Annual flame retardant growth rate for each major market is also projected. Toxicity data are reviewed on only those compositions that are considered commercially significant today. This includes 18 compounds or families of compounds and four inherently flame-retarded polymers. Toxicological studies of flame retardants for most synthetic materials are of recent origin and only a few of the compounds have been evaluated in any great detail. Considerable toxicological problems may exist in the manufacturing of some flame retardants, their by-products, and possible decomposition products.

Repeated chlorpromazine administration increases a behavioural response of rats to 5-hydroxytryptamine receptor stimulation. 1 The hyperactivity syndrome produced in rats by administration of tranylcypromine (20 mg/kg i.p.) followed 30 min later by L-tryptophan (50 mg/kg i.p.) is generally considered to be due to increased 5-hydroxytryptamine (5-HT) functional activity. It is inhibited by chlorpromazine (30 mg/kg i.p.) injected 60 min before the tranylcypromine. However, chlorpromazine injection for 4 days either at a dose of 30 mg/kg once daily or 5 mg/kg twice daily results in an enhanced hyperactivity response to tranylcypromine and L-tryptophan administration 24 h after the final dose of chlorpromazine. 2 One injection of chlorpromazine (30 mg/kg) did not produce enhancement 24 h later and the inhibition of the tranylcypromine/L-tryptophan hyperactivity observed after acute chlorpromazine injection was seen if the rats were given tranylcypromine and L-tryptophan 1 h after the fourth chlorpromazine (30 mg/kg) dose. 3 Chlorpromazine (30 mg/kg) once daily or 5 mg/kg twice daily for 4 days resulted in rats displaying enhanced behavioral responses to the suggested 5-HT agonist 5-methoxy N,N-dimethyltryptamine (2 mg/kg) on day 5. 4 Chlorpromazine (30 mg/kg) once daily for 4 days produces a slight increase in brain 5-hydroxytryptamine (5-HT) concentration on day 5, but no difference in the rate of brain 5-HT synthesis or the rate of 5-HT accumulation after tranylcypromine and L-tryptophan administration. 5. There is some evidence that chlorpromazine blocks 5-HT receptors. It has also been observed that several other neuroleptic drugs do not produce enhanced 5-HT responses after repeated administration. It is suggested therefore that the enhanced behavioural response to 5-HT receptor stimulation following repeated chlorpromazine administration may be because this drug blocks 5-HT receptors.

Vascular reactivity to angiotensin II infusion during gestation. We serially tested 26 healthy, young, nulliparous patients, while they were maintained in the left lateral recumbent position, during a four-week interval (29 to 32 weeks), with progressive increments of angiotensin-II (A-II) 2.0 to 15.0 ng. per kilogram per minute). Blood pressure was recorded with an ultrasound device. All patients were followed through delivery. Three patients (12 per cent) developed pregnancy-induced hypertension (PIH); only one of these demonstrated enhanced vasoreactivity prior to PIH. Conversely, 13 patients who did not develop PIH demonstrated enhanced vasoreactivity at least once during the testing interval. Comparison of results obtained from one week to the next was evaluated in 57 test pairs; discordant data, i.e. reaction to less than 8 ng. per kilogram per minute one week and nonreaction the next, was observed in 17 pairs (30 per cent). We conclude that assessment of the risk of PIH, with the use of the diastolic pressor response to infused A-II, is unreliable.

[The evolutionary changes in the amino acid sequences and properties of the ATP-synthase in chloroplasts, mitochondria and bacteria]. Studies have been made on ATPase from chloroplasts, cyanobacteria and mitochondria of higher plants and animals. No intraspecies and interspecies variability of chloroplast and mitochondrial ATPase was found with respect to pH optimum of the activity, to specificity to cations as substrate components, to sensitivity to stimulating and inhibiting anions and ethanol, to optimal stimulating ethanol concentration. Intergenus variation of these properties of ATPase from chloroplasts, plant mitochondria, and cyanobacteria was revealed. Analysis of homology of the amino acid sequence in ATP-synthase subunits showed that ATP-synthase genes in chloroplast DNA originate from cyanobacterial genome, whereas ATP-synthase genes in plant and animal mitochondria-from genome of Rhodospirillum rubrum or closely related species. It was established that no recombination between the genetic material of chloroplasts and mitochondria took place during evolution.

Cyclosporine-responsive granulomatous sebaceous adenitis in a dog. Granulomatous sebaceous adenitis was diagnosed in a 2 year old spayed Miniature Pinscher. Initial treatment with isotretinoin for 3 weeks resulted in little response and decreased tear production. Immunosuppressive doses of prednisone for 3 weeks resulted in mild response of the dermatitis; however, the dog developed transient diabetes mellitus secondary to this treatment. Cyclosporine (5 mg/kg of body weight, po, q 12 h) resulted in good clinical response for 12 months, but histologically, the sebaceous glands remained absent. Although cyclosporine has immunosuppressive properties, this drug also has inhibitory effects of keratinocyte proliferation. These mechanisms may explain the beneficial response of cyclosporine in the treatment of granulomatous sebaceous adenitis in this dog.

[Prognostic significance of the CA 125 half-life for the further outcome of ovarian cancer]. Since only approx. 30% of patients with ovarian carcinoma present themselves in the early stages, and as a result of the lack of effective screening methods, primary interest has been applied to the improvement of the treatment quality in the later stages. Improvement of therapeutic strategies implies an adaptation of specific characteristics of the patient and the tumour. For instance, in cases of primary progression during chemotherapy, it is not justified to continue an aggressive treatment, which causes additional serious side effects. Surprisingly, it has not been possible, to utilize established or suspected prognostic factors for treatment strategies in ovarian cancer. This might result, in part, from the uncertainty of criteria such as stage of disease, residual tumour and histological grading. The single most relevant prognostic factor today is the residual tumour mass. In 1988 van der Burg suggested for the first time a potential prognostic relevance of the CA 125 half-life. This study was designed, to investigate the use of CA 125 half-life in therapeutic strategies. From January 1984 to June 1990, 346 patients with primary ovarian cancer were treated at our institution. Preoperative CA 125 levels were determined in 292 patients; in 220 patients the levels were complete for a period of more than 6 months so that the CA 125 half-life could be calculated. Survival times of patients with a half-life of less than 20 days were significantly (p less than 0.0001) different from patients with a half-life of more than 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Alternative statistical techniques to evaluate linearity. With the increase in demand for linearity assessment, a wide variety of analysis techniques have been advocated. There is no consensus on optimal techniques. This article reviews different approaches that have been advocated by the College of American Pathologists, by the National Committee for Clinical Laboratory Standards, and by manufacturers of diagnostic methods and controls. This is not a review of all statistical techniques proposed for linearity assessment. I discuss four basic categories of methods, with the first and simplest being visual review. The second general approach includes the conventional statistical techniques based on least-squares regression; this includes an equation for the line and statistical tests for linearity and for curvature. The third general approach involves comparison of slopes for line segments, or "deltas." This approximates the visual assessment of linearity. The fourth approach involves comparing observed and expected values, with some allowance for differences. Comparisons can be made for observed single results, means of replicates, or components of variance. Allowances for error can be internal goals or goals that are recommended for clinical usefulness. Each approach has strengths in different aspects of linearity assessment, including intuitive appeal, statistical rigor, and objectivity. Similarly, each approach has limitations that are not always obvious.

A simple and sensitive bioassay method for detection of EDRF with RFL-6 rat lung fibroblasts. Detailed characteristics of a new bioassay method for detection and quantification of endothelium-derived relaxing factor (EDRF) are described. Guanosine 3',5'-cyclic monophosphate (cGMP) responses of RFL-6 rat fetal lung fibroblast cells were utilized to estimate the activity of nitric oxide (NO) and EDRF. The conditioned medium from bovine aortic endothelial (BAE) cells cultured in tissue culture plates was quickly transferred to RFL-6 incubations to determine EDRF. In the presence of superoxide dismutase, RFL-6 cells cultured in six-well tissue culture plates exhibited very high sensitivities to both NO and EDRF; e.g., they responded to NO at a concentration as low as 2 nM and the basal release of EDRF from 1-2 X 10(6) BAE cells. Based on the lower detection limit of the radioimmunoassay for cGMP, calculations reveal that 100-200 fmol of NO and the basal EDRF release from 1-2 X 10(5) BAE cells can be detected with RFL-6 cells by choosing smaller culture wells. Thus this method is more sensitive than any other currently available. Furthermore, it may be widely used, since the instrumentation required is presently available in many laboratories. This bioassay technique for EDRF and NO is sensitive, simple, and quite useful for the evaluation of experimental conditions and compounds that regulate EDRF release from various endothelial cells and tissues.

Cloning and expression of a human 14-3-3 protein mediating phospholipolysis. Identification of an arachidonoyl-enzyme intermediate during catalysis. The major phospholipase A2 activity in sheep platelets is mediated by at least three chromatographically resolvable isoforms of a 30-kDa dimeric polypeptide which are responsive to physiologic increments in calcium ion and possess a dramatic substrate selectivity (Loeb, L. A., and Gross, R. W. (1986) J. Biol. Chem. 261, 10467-10470). Herein, we describe the cloning and expression of the human equivalent of one such isoform and demonstrate that it catalyzes the cleavage of the sn-2 fatty acid of choline and ethanolamine glycerophospholipids through the formation of a stable acyl-enzyme intermediate. Transesterification of the sn-2 acyl group of phosphatidylcholine to the recombinant 30-kDa polypeptide is over 50-fold selective for arachidonic acid, is augmented by calcium ion, and results in the formation of an arachidonoyl-thioester intermediate. Homology analysis demonstrated that the polypeptide mediating this transesterification is one member of a family of proteins collectively designated as 14-3-3 proteins. These results demonstrate that at least one intracellular mammalian phospholipase A2 employs a catalytic strategy distinct from that utilized by extracellular phospholipases A2 (i.e. formation of an acyl-enzyme intermediate by nucleophilic attack versus activation of a water molecule) and that arachidonic acid in endogenous phospholipid storage depots can, in principle, be sequentially transferred through an acyl-enzyme intermediate without the prior obligatory release of free arachidonic acid.

[The open-field, non-stressed behavior of rats under the acute and chronic effect of imipramine and tranylcypromine, depending on the individual reaction type (emotional and non-emotional)]. The acute and prolonged effects of imipramine and tranylcypromine were studied on 30 emotive and 30 non-emotive mature male Wistar rats to determine whether the drugs affect the behavior of these two reaction types differently. We found that both drugs change the typical behavior of the rats in the open field, each in a different way. Acute doses of imipramine inhibit symptoms of anxiety as well as the exploratory behavior so that the rats appear totally disinterested in their environment. This finding seems to confirm the assumed central nervous suppressing effects of this drug as mentioned in the literature. Single doses of tranylcypromine have effects similar to those mentioned for imipramine; however, long-term use results in a "vitalisation" of behavior: symptoms of anxiety remain inhibited and exploratory behavior becomes dominant. Both drugs produced a certain "flattening" of behavior. Due to the effects of drugs used, the original behavioral differences without stress disappear. Prolonged use of tranylcypromine makes emotive rats totally non-emotive.

The effect of hypercholesterolemia on SEPs recorded from rats. Twenty-four albino rats, weighing 180-200 g were studied. Twelve of them were fed with a diet containing 1% cholesterol for 12 weeks and the others were fed with a normal lab diet for the same period. As a result, plasma cholesterol level was found in the diet group 134.04 +/- 21.11 mg/dl with respect to control 72.72 +/- 10.5 mg/dl. In the two groups, following left posterior tibial nerve (PTN) stimulation, SEPs were recorded from central (Cz) referenced to frontal (Fz). In the hypercholesterolemic group, the first negative component (N24) was found to be prolonged (p less than .001) and the peak-to-peak amplitudes (N24P40, P40N80) were observed to be decreased (p less than .001). These results have shown that the latency and amplitude can be changed by hypercholesterolemia.

The renin-angiotensin systems in adrenal-regeneration hypertension. Adrenal regeneration hypertension [ARH] was induced after Ingle and Higgins, and Skelton in 13 female Wistar rats one and a half months old with the purpose of studying the function of the renal and the brain renin-angiotensin systems in that model of hypertension, before and after treatment with antihypertensive prostaglandin EI [PGEI]. It was found that a 30 days' application of PGEI induced a regression of the regenerated adrenal cortex, accompanied by a significant decrease in arterial blood pressure to normotensive values. Plasma renin activity did not correlate with the level of the blood pressure nor with kidney renin activity and was not influenced by PGEI. However renal renin activity, which was found to be increased, corresponded to the elevated blood pressure, and decreased almost to normal values with normalization of the blood pressure. A correlation between the brain and kidney renin systems was established in that increased renal renin activity was accompanied by low brain stem and medulla renin activity. The balance was restored by PGEI, which not only lowered blood pressure and decreased renal rein acitivity, but induced an increase of brain stem and medulla renin activity. It is concluded that there exists a notable connection between adrenal cortex regeneration, renal antihypertensive prostaglandins and the kidney and brain renin-angiotensin systems, which pays a correlated role in the mechanism of adrenal regeneration hypertension.

Temperature-sensitive variants of Saccharomyces cerevisiae iso-1-cytochrome c produced by random mutagenesis of codons 43 to 54. In vitro random mutagenesis within the CYC1 gene from the yeast Saccharomyces cerevisiae was used to produce a library of mutants encompassing codons 43 to 54 of iso-1-cytochrome c. This region consists of an evolutionarily conserved structure within an evolutionarily diverse sequence. The library, on a low-copy-number yeast shuttle phagemid, was introduced into a yeast strain lacking cytochrome c. The ability of transformants harboring a functional cytochrome c to grow on the non-fermentable carbon source glycerol at 30 degrees C and 37 degrees C was used to determine the phenotype of nearly 1000 transformants. Approximately 90% of the missense mutants present in the library give rise to the wild-type phenotype, 7% result in the temperature-sensitive (Cycts) phenotype, and 3% give rise to the non-functional (Cyc-) phenotype. Phagemids from 20 Cycts and 30 Cyc- transformants were subjected to DNA sequence analysis. All the mutations occur within the targeted region. One-third of the mutants from Cyc- transformants and all the mutants from Cycts transformants are missense mutants. The remaining mutants from Cyc- transformants are nonsense or frame-shift mutants. Missense mutations within the codons for Gly45, Tyr46, Thr49, Asn52 or Ile53 alone are sufficient to produce temperature-sensitive behavior both in vivo and in the variant proteins. The deduced amino acid substitutions correlate remarkably well with side-chain dynamics, secondary structure and tertiary structure of the wild-type protein.

The mitochondrial genome of an exsymbiotic Chlorella-like green alga. Mitochondrial (mt) DNA from the unicellular, exsymbiotic Chlorella-like green alga, strain Nla was isolated and cloned. The mtDNA has a buoyant density of 1.692 g/ml in CsCl and an apparent G/C base composition of 32.5%. The genome contains approximately 76 kbp of DNA based on restriction fragment summation and electron microscopic measurements. A map of restriction endonuclease sites using Sst I, Bam I, Sal I and Xho I was generated. The genome maps as a circular molecule and appears as such under the electron microscope. Eight genes were assigned to the map by hybridization to specific restriction fragments using heterologous mt-encoded specific probes. These include the genes for subunits 6, 9, and alpha of the F0-F1 ATPase complex, the large and small subunit rRNAs, cytochrome oxidase subunits I and II, and apocytochrome b.

Energy expenditure, lipolysis, and glucose production in preterm infants treated with theophylline. Theophylline is administered to preterm infants with pulmonary disease to improve pulmonary function and reduce apneic episodes. Because it potentially mediates both alpha- and beta-receptor-effector mechanisms, we tested the hypothesis that it increases lipolysis, gluconeogenesis from glycerol, and energy expenditure in 16 preterm infants, eight of whom were treated therapeutically with theophylline for apnea of prematurity (T) and eight of whom were controls (C). Mean +/- SD postnatal ages were 4.8 +/- 1.9 wk (T) and 2.4 +/- 0.9 wk (C) (p < 0.01). Corrected gestational ages were 35 +/- 1.6 wk (T) and 34 +/- 0.5 wk (C) (p = NS). Body weights were 1.69 +/- 0.13 kg (T) and 1.70 +/- 0.23 kg (C) (p = NS). All infants were clinically stable, breathing room air, fed enterally, and receiving no diuretics, steroids, or antibiotics. Lipolysis, hepatic glucose production, and gluconeogenesis from glycerol were measured using [2-13C]glycerol and [6,6-3H2] glucose tracers. Body water and energy expenditure were measured by the 2H2(18)O method. Body water volumes were 68.5 +/- 3.4% body weight (T) and 70.2 +/- 3.4% (C) (p = NS), suggesting fat was 10-13% of body weight in both groups. Mean daily energy expenditure was 65 +/- 22 kcal/kg body weight/d (T) versus 59 +/- 5 kcal/kg body weight/d (C) (p = NS). Between 4 and 6 h after a feeding, glucose production rates were 40.5 +/- 4.3 mumol/kg/min (T) and 37.6 +/- 4.8 mumol/kg/min (C) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Vasopressin and fetal cerebrovascular regulation. Vasopressin (AVP) may increase cerebral blood flow (CBF) during hypoxemia by selective dilatation of cerebral vessels via endothelium-derived relaxing factor (EDRF) release. To test whether this action is relevant in the fetus, we produced isocapnic hypoxemia in halothane-anesthetized pregnant ewes. Fetal infusion of a V1 AVP antagonist reduced by 55% the increase in CBF during fetal hypoxemia. To test the role of this response during development, we examined the response to AVP in intact and endothelium-denuded femoral and basilar arterial rings in vitro from fetal, newborn, and adult sheep. AVP constricted femoral rings in an endothelium-independent manner, with increased potency in newborn and fetal compared with adult rings. AVP relaxed basilar rings in an endothelium-dependent manner, which was unaffected by indomethacin treatment, with increased potency in newborn and adult compared with fetal rings. We conclude that fetal cerebral vascular endothelium is functional and responsive to AVP and that circulating AVP during fetal hypoxemia contributes to increased CBF via this effect.

Studies on metatherian sex chromosomes II. The improbability of a stable balanced polymorphism at an X-linked locus with the paternal X inactivation system of kangaroos. Female kangaroos and perhaps other female marsupials have a unique form of dosage compensation for X-linked genes in their soma. In these animals the paternal X is inactive. Heterozygote females therefore have the phenotype of one or the other of the homozygotes, with the allele which is expressed coming from their mother. The unexpressed paternally derived allele may, however, be transmitted to the next generation in the usual Mendelian manner and there be expressed. Such a combination of haploid phenotypic expression and diploid genotypic behaviour on the part of X-linked genes in kangaroos makes their population genetics unique. This paper examines the possibilities for balancing selection in the kangaroo X chromosome system and shows that balanced polymorphisms are unlikely to occur. If 1 - a, 1, 1 - b and 1 are the selection coefficients of the alpha1 females, alpha2 females, alpha1 males and alpha2 males respectively (where alpha1 is the phenotype when A1 is expressed and alpha2 the phenotype when A2 is expressed), then the equilibrium is reached when the gene frequency of A1 in females = 0-5(a-1 + b-1), which takes values between 0 and 1 for only a few of the biologically likely values of a and b.

Gene expression of an Escherichia coli ribosomal RNA promoter fused to structural genes of the galactose operon. The promoter region of the rrnB ribosomal RNA gene of Escherichia coli has been ligated within the epimerase gene (galE) of the galactose operon in a lambda phage vector. The recombinant lambda phage has been characterized by restriction mapping and assays of both galK (galactokinase) gene activity and galactose messenger RNA hybridization. In such lyosgens, expression of the fused galactose operon occurs as a function of growth rate in a manner characteristic of ribosomal RNA gene expression and is subject to stringent control by amino acid availability for protein synthesis. Galactose messenger RNA arising from the ribosomal promoter is not as metabolically stable as ribosomal RNA.

The effect of remobilisation on the extremity of the adult rat after short-term immobilisation in a plaster cast. The one hind leg of adult male rats was immobilised for 4 weeks in a plaster cast. The cast was then removed and the leg was subsequently remobilised for 4 and 16 weeks respectively. Studies of the skeletal mass of the femur and the tibia from the immobilised leg showed that after 4 weeks of remobilisation there were still clear signs of osteoporotic changes of the bones as compared with the corresponding bones from control non-immobilised rats. After 16 weeks of remobilisation there were no esteoporotic changes detectable by the methods used.

Differential diagnosis of inflammatory bowel disease. A comparison of various diagnostic classifications. Fifty consecutive patients with inflammatory bowel disease of the colon who presented at the University Hospital Rotterdam/Dijkzigt were assessed by four methods: clinical diagnosis, criteria defined by Lennard-Jones and by the Organisation Mondiale de Gastroenterologie (O.M.G.E.) scoring systems, and histologic slide review. All cases were classified into three diagnostic groups: established Crohn's disease (CD), indeterminate colitis, or definite ulcerative colitis (UC). The classifications were compared by kappa analysis. Eighteen of the 50 patients were classified as having established CD by the O.M.G.E. scoring system and Lennard-Jones criteria; 17 were so classified by clinicians, and only 8 by histologic slide review. The agreement among clinician's diagnosis, Lennard-Jones criteria, and the O.M.G.E. scoring system was good (Fleiss-Cohen-weighted kappa; p less than 0.001). Agreement among histology, Lennard-Jones criteria, and the O.M.G.E scoring system was less good (p less than 0.05) and not significantly associated with clinical diagnosis. Histology was less prone to diagnose established CD or established UC and more likely to diagnose indeterminate colitis. This study has shown that the systems of disease definition set out by Lennard-Jones and the O.M.G.E. are comparable and agree well with each other and clinicians's diagnosis, but biopsy specimens have a limited diagnostic value in disease differentiation in inflammatory bowel disease.

Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1. The induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation. We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule (AIM)/CD69 activation pathway. Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb. Mobility shift assays showed that addition of anti-AIM mAb to PMA-treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence, the phorbol ester response element. In contrast, anti-AIM mAb did not induce any change in the binding activity of NF-kappa B, a transcription factor whose activity is also regulated by protein kinase C. The increase in AP-1-binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun. Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb. Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide, suggesting that de novo protein synthesis is crucial for the induction of AP-1-binding activity. These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1. Therefore, this pathway appears as a crucial step in the initiation of early T cell activation events.

Correlation of amniotic fluid glucose concentration and intraamniotic infection in patients with preterm labor or premature rupture of membranes. Amniotic fluid glucose concentration has previously been suggested as a rapid and sensitive test for diagnosing intraamniotic infection. In this study, 204 patients less than or equal to 34 weeks estimated gestational age with preterm labor or premature rupture of membranes underwent amniocentesis to detect subclinical intraamniotic infection. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for Mycoplasma species. Amniotic fluid glucose levels were significantly lower in patients with positive amniotic fluid cultures than in patients with negative cultures (median, 10 mg/dl; range, 1 to 62 mg/dl vs median, 31 mg/dl; range, 2 to 126 mg/dl, respectively; p less than 0.001). In terms of predicting amniotic fluid culture results, an amniotic fluid glucose concentration of less than or equal to 16 mg/dl had a sensitivity of 79%, specificity of 94%, positive predictive value of 87%, and negative predictive value of 90%. The determination of amniotic fluid glucose concentration is useful in detecting subclinical intraamniotic infection in patients less than or equal to 34 weeks estimated gestational age with preterm labor or premature rupture of membranes.

Normalization and its relevance today. Historically, the normalization principle has been influential in promoting a comprehensive community-based service delivery system for people with developmental handicaps. However, its effects were more positive a decade ago when the issues were simply inhumane institutions or more individualized community-based alternatives. Issues in community-based programs for developmentally handicapped people have become more diverse and the choices more complex. In the current climate, the effects of the normalization principle have polarized issues for several reasons: The theory works better than current practice, the criteria are vague and the goals unattainable, normalization takes the focus away from individual client needs, the theory discourages diversity, normalization has become a rallying point for inappropriate practices, overzealousness of normalization advocates has polarized issues, normalization promotes an undesirable value system, and normalization ignores handicapped clients' deficits. What is needed to replace the normalization principle today are guiding concepts that are clearer, more responsive to client needs, and more reflective of value systems that are in the best interests of handicapped people.

Relationship between phosphate content and immunochemical properties of subfractions of bakers' yeast mannan. The mannan of bakers' yeast (Saccharomyces cerevisiae) was fractionated on a column of diethylaminoethyl-Sephadex into five subfractions. Phosphate content of these mannan subfractions was proportional to the concentration of NaCl solutions used in the chromatographic separation. Quantitative precipitin reactions showed that the serological reactivities of the subfractions were proportional to the content of phosphate. The result of acetolysis study showed that the amounts of mannotetraose and phosphate-containing oligosaccharide fractions increased proportionally to the acidity, whereas the amount of mannose decreased inversely. The results from quantitative precipitin reaction tests and acetolysis study demonstrated that both phosphate contents and multiplicity of branching moieties of mannan subfractions increased proportionally, i.e., micro-heterogeneity concerning the acidity comprised in the parent bulk mannan is not attributable merely to the coexistence of molecular species containing different amounts of phosphate but also to the presence of more of the branching moieties.

Delayed time to peak serum myoglobin level as an indicator of cardiac dysfunction following open heart surgery. Postoperative changes in serum myoglobin levels have been studied in 47 patients undergoing open heart surgery. The patients were retrospectively divided into two groups according to the time to peak myoglobin level during reperfusion. In 38 patients, myoglobin levels increased rapidly to a peak within 3 hours after reperfusion, after which it was cleared from the blood (group 1). Contrarily, a rise in myoglobin levels was persistent for 24 hours and its time to peak was greater than 3 hours after reperfusion in nine patients (group 2). There were no differences in preoperative and early reperfusion (within 1 hour of reperfusion) values of myoglobin between the two groups. At 3, 6, and 12 hours of reperfusion, myoglobin levels were significantly greater in group 2: 448 +/- 196 vs 1,149 +/- 900 ng/ml, 359 +/- 172 vs 2,653 +/- 3,179 ng/ml, 184 +/- 95 vs 1,896 +/- 1,387 ng/ml, respectively, p less than 0.0001 in each. The maximum activities of both myoglobin and CK-MB were significantly higher in group 2 (myoglobin-max: 771 +/- 257 vs 3,221 +/- 3,024 ng/ml, p less than 0.0001; CK-MBmax: 107 +/- 60 vs 227 +/- 219 IU/L, p less than 0.005). Five of nine patients in group 2 required post-operative assistance with intra-aortic balloon pumping (p less than 0.0005 compared with one of 38 in group 1) and perioperative myocardial infarction developed in three patients (33.3 percent) in this group (p less than 0.005 compared with 0 percent in group 1). Thus, patients with a delayed peak of serum myoglobin level exhibited detrimental cardiac failure postoperatively. These findings suggest that myocardial injury accelerated by reperfusion following ischemia might progress in these patients.

[The peripheral hemodynamics of pregnant women with diabetes mellitus]. The state of the peripheral hemodynamics was studied rheovasographically in 26 pregnant patients suffering of diabetes mellitus and 30 healthy pregnant (pregnancy terms: 26, 27 and 34-40 weeks). Results of the study revealed changes of the peripheral hemodynamics in the pregnant diabetic patients as compared with pregnant women non-diabetics. These changes consisted in non-adequate response of the vascular bed to increased hemodynamic loads at the 27-33 pregnancy week as well as in more significant increase of the tone in the diabetic patients during the first half of pregnancy as compared with the healthy women. These changes may become supplementary criteria for revealing preclinical manifestations of diabetic angiopathies in pregnant diabetic women.

Regulation of parathyroid cell gene expression in experimental uremia. The secondary hyperparathyroidism of renal failure is an important component of renal osteodystrophy. We studied PTHmRNA levels and their regulation in control and subtotal nephrectomized (5/6 NX) rats at 3 wk, as well as levels of the 1,25(OH)2D3 receptor mRNA in parathyroids. Serum 1,25(OH)2D levels were decreased in 5/6 NX, whereas PTHmRNA levels were increased (7 +/- 0.7 OD U, N = 4) compared to controls (2.1 +/- 1.2, P less than 0.01); both decreased after 1,25(OH)2D3 (100 pmol/100 g body weight). Similar results were found in 5/6 NX rats after 3 months. There was no change in actin mRNA levels. PTHmRNA levels were highest in 5/6 NX rats with the most severe renal failure. The parathyroid gland 1,25(OH)2D3 receptor mRNA levels were not different between 5/6 NX rats and controls and were not affected by 1,25(OH)2D3 (100 pmol/100 g body weight daily) at 1 or 3 days. PTHmRNA levels of 5/6 NX rats did not increase when the serum calcium was decreased from 2.8 +/- 0.05 mmol/L to 0.9 +/- 0.15 mmol/L at 3 or 5 h, which contrasted with the marked increase in PTHmRNA in normal rats after hypocalcemia. As in normal rats, after hypercalcemia (4.8 mmol/L at 1 h) there was no change in the 5/6 NX rats' PTHmRNA levels. These results show that 5/6 NX rats have increased PTHmRNA levels that are normally regulated by injected 1,25(OH)2D3 but not by calcium. Parathyroid gland 1,25(OH)2D receptor mRNA levels are not increased in 5/6 NX in contrast to the increased PTHmRNA, which reflects the larger glands of uremia. 1,25(OH)2D receptor mRNA levels were not regulated by 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Factors related to accuracy in office cholesterol testing. Iowa Academy of Family Physicians Research Network. There has been growing interest in the performance of diagnostic testing in physician office laboratories (POLs). Since the measurement of cholesterol is a well-defined and standardized laboratory test, it was selected to assess factors related to test accuracy in POLs. One hundred thirty-one family practice offices were eligible to participate in the survey. Each was mailed a cholesterol specimen with a standardized value in October 1988. The laboratory characteristics of those POLs with results that were within 10% of the true specimen value were compared with those with results that were greater than 10% in error. Of the 131 POLs, 122 returned an answer for the unknown specimen. Ninety-eight (80%) were within 10% of the true value, and 114 (93%) were within 15%. Factors that were related to lower error rates (more likely to be within 10% total error) were whether the laboratory performed more than 25 laboratory tests per day, participated in a proficiency testing program, and ran daily quality controls, as well as the type of instrument the laboratory used. Overall performance of the POLs compared favorably with reference laboratories; however, running controls and participating in a proficiency testing program may further improve POL test accuracy.

[The materials and border-zone micromorphology of a glass-ionomer cement cavity lining material]. The combination of various possibilities for sample preparation and investigation--the tinting penetration method, the ion beam slope cutting, the light and scanning electron microscopy--allow statements at the grind after different drying of the preparation mainly to the bond but also surface and filler shape of glass-ionomer cements. The dentine in the area of enamel-dentine-junction and of superficial root area is effectively closed by Ketac-Bond. Likewise, the bond with cover filling (Visio-Molar) can be considered without gaps except a single case. Crack propagations from the cement surface seem to related to pores and occur independently of type of drying especially in case of mechanical after treatment of already hardened cavity lining [correction of underfilling] material.

A DNA replication enhancer in Saccharomyces cerevisiae. We have dissected the autonomously replicating sequence ARS121 using site-directed in vitro mutagenesis. Three domains important for origin function were identified; one of these is essential and contains an 11-base-pair sequence resembling the canonical ARS core consensus; the second region, deletion of which affects the efficiency of the origin, is located 3' to the T-rich strand of the essential sequence and encompasses several elements with near matches to the ARS core consensus; the third region, containing two OBF1 DNA-binding sites and located 5' to the essential sequence, also affects the efficiency of the ARS. Here we demonstrate that a synthetic OBF1 DNA-binding site can substitute for the entire third domain in origin function. A dimer of the synthetic binding site, fused to a truncated origin containing only domains one and two, restored the origin activity to the levels of the wild-type ARS. The stimulation of origin function by the synthetic binding site was relatively orientation independent and could occur at distances as far as 1 kilobase upstream to the essential domain. Based on these results we conclude that the OBF1 DNA-binding site is an enhancer of DNA replication. We suggest that the DNA-binding site and the OBF1 protein are involved in the regulation of the activation of nuclear origins of replication in Saccharomyces cerevisiae.

Characterization of accessory cell function during acute infection of BALB/cByJ mice with mouse hepatitis virus (MHV), strain JHM. Earlier studies revealed defective concanavalin A-stimulated proliferation and cytokine production by spleen cells derived from BALB/cByJ mice acutely infected with mouse hepatitis virus (MHV), strain JHM. Based on those observations, assays of in vitro antigen-presenting cell (APC) function were undertaken. APC function of unfractionated spleen cells from individual MHV-infected mice was highly variable. Experiments using pooled spleen cells derived from MHV-infected mice revealed that adherent spleen cell APC function was impaired to a much greater degree than B cell APC function. Adherent cells derived from peritoneal exudates of infected mice exhibited an APC defect that was similar in magnitude to that observed for splenic adherent cells. Splenic B cells derived from acutely infected BALB/cByJ mice harbored infectious MHV. In contrast, lysates of adherent spleen cells from acutely infected mice did not kill intracerebrally inoculated neonatal mice, but did induce seroconversion among all survivors. Despite impairment of APC function of cells derived from MHV-infected donors, neither indomethacin nor accessory cells from uninfected control mice restored concanavalin A-induced proliferative responses of spleen cells collected from acutely infected mice. These results and those of earlier studies suggest that, although APC function is impaired, in vitro T cell dysfunction exhibited by spleen cells from MHV-JHM-infected donors is probably related to an inherent proliferative defect subsequent to T cell activation. Defective concanavalin A-stimulated proliferation does not appear to be secondary to accessory cell function suppression or to inhibitory factors secreted by accessory cells.

Different patterns of inhibition of adrenaline-induced platelet aggregation and kinetics in vivo by acetylsalicylic acid and indobufen. The inhibitory effect of 50 mg/kg lysyl acetylsalicylic acid (ASA) intravenously injected 24 and 4 h before 80 micrograms/kg adrenaline, 40 mg/kg indobufen injected 15 min before, or a combination of ASA plus indobufen on the platelet aggregation and kinetics was evaluated in anaesthetized dogs previously injected with 111indium- (111In-) labelled platelets using gamma-camera dynamics studies. The highest degree of inhibition, indicated by the lowest platelet aggregation ratio decrease and the most significant 111In-labelled platelet mobilization from hepatic and splenic stores with a corresponding increase of labelled and unlabelled platelet counts in blood, was obtained in ASA-treated dogs. Such changes were less marked when ASA plus indobufen was injected. In indobufen-treated dogs a similar mobilization of 111In-labelled platelets with an increase in circulating platelet numbers was evident only after the second adrenaline injection. It is concluded that platelet mobilization is mainly dependent on the production of an ASA-sensitive substance.

Epitope mapping studies of snake venom phospholipase A2 using monoclonal antibodies. Fifteen different monoclonal antibodies developed against pseudexin, a snake venom phospholipase A2 with presynaptic neurotoxicity, were screened for linear epitope recognition. Peptides (9-mers) spanning pseudexin were synthesized by using alanine-derivatized polyethylene pins and subsequently probed with antibody. Four antibodies bound to toxin peptides and were detected with an enzyme-linked immunosorbent assay. Three of the bound antibodies recognized a site important in calcium binding and the interlocking of dimeric forms of snake venom phospholipase A2. Analogous regions from other phospholipases were synthesized and probed with the four reactive antibodies. A good correlation was found between the reactivity of whole molecule phospholipases and peptide regions with the antibodies. Monoclonal antibodies neutralizing the lethal or enzymatic effects of pseudexin did not recognize any linear epitopes.

[Interfering and interferonogenic activity of attenuated and original para-influenza viral strains]. A higher interfering activity of attenuated (vaccine) strains of parainfluenza virus types 1, 2 and 3 which had undergone a long-term adaptation to cell cultures as compared to the original viruses was established. The interferon-inducing activity of vaccine parainfluenza virus types 2 and 3 was also higher than that of the original viruses. The high interfering and interferon-inducing activity of attenuated parainfluenza virus strains of type 2 and 3 correlated with reduced virulence of these variants for man. These tests may be used for the assessment of virulence of parainfluenza virus strains type 2 and 3 in the laboratory.

Surgical evaluation of the modified Fontan procedure. From 1980 to 1990 152 patients underwent Fontan operation at our institution. The following patient groups were identified: 1. patients with tricuspid atresia (n = 82, 54.0%); 2. patients with single ventricle (n = 31, 20.3%); 3. patients with a wide variety of non correctable, complex cardiac malformations (n = 39, 25.7%). In 27.0% of the patients a primary Fontan operation was performed. 45.0% of the patients received a previous shunt to increase pulmonary blood flow and in 29.4% of the patients a pulmonary artery band was placed to reduce pulmonary flow. Overall mortality was not significantly different in patients with previous palliative procedures (19.4%, n = 18) as compared to 17.4% (n = 6) in patients with primary Fontan operation. Risk of death was high in the group with complex cardiac malformations (28.2%, n = 11) and in patients with single ventricle (19.4%, n = 6). Early mortality was considerably less in patients tricuspid atresia (8.5%, n = 7). Postoperatively patients with incorporation of the residual right ventricular chamber and pulmonary valve (Fontan-Bjoerk) showed a significant (p less than 0.05) lower incidence of pleural effusion as compared to patients with other modifications of the Fontan procedure. Actuarial survival rate of all patients is 83.8 +/- 3.1% (mean +/- SEM) at ten years. The modified Fontan procedures are providing an accepted surgical method for patients with otherwise non correctable cardiac malformations.

Physiological effects of altitude training on elite male cross-country skiers. Seven elite male cross-country skiers trained for 3 weeks at an altitude of 1900 m. Haemoglobin concentration ([Hb]), haematocrit (Hct) (obtained from venous blood), maximal oxygen uptake (VO2 max) and energy expenditure during a standard submaximal workload were measured before and after training at altitude, and 1 year later while training at sea level (control). Both [Hb] and Hct increased significantly, and the skiers with the lowest initial [Hb] and Hct experienced the largest increases during training at altitude. The increase in blood lactate (BLa) concentration (using haemolysed capillary blood) during a standard submaximal exercise test was significantly lower after training at altitude than before it or 1 year later (control). A significant correlation was found between the magnitude of increase in [Hb] and Hct and the difference in the lactate response to the standard submaximal workload pre- and post-altitude training. Although VO2 max remained unchanged, lower BLa concentration during the submaximal test probably reflects an improved ability to exercise at higher submaximal workloads shortly after training at altitude compared with pre-altitude training. It is suggested that subjects with low initial [Hb] and Hct improve their aerobic performance capacity most during altitude training.

Evaluation of antiproliferative agents using a cell-culture model. Chinese hamster ovarian (CHO) cells in culture were used to evaluate the relative antiproliferative potential of drugs. These agents have been used to improve the clinical response after glaucoma filtering surgery. The following drugs were evaluated: 5-fluorouracil (5-FU) as the benchmark, 5-fluorouridine (FUR), 5-fluorodeoxyuridine (FUDR), 5'-deoxy-5-fluorouridine (DFUR), bleomycin, and cytarabine (ARA-C). In addition to cell counting, a colorimetric assay based on the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to follow growth response. The MTT assay was found to be extremely convenient and an indirect measure of cell activity, offering an alternate or addition to a measure of cell number. All agents tested were shown to inhibit cellular proliferation. Dose-response curves for each agent indicate the following absolute potency: FUDR greater than FUR greater than ARA-C greater than 5-FU = bleomycin greater than DFUR. Besides absolute potency, an evaluation of the effects of equivalent inhibitory concentrations of each drug on growth rate was assessed. Several agents affected the proliferation rate patterns differently. Based on these studies, it is suggested that the in vitro model can identify potential agents through an assessment of their overall activity profile in CHO cells, which includes not only their potency based on dose response, but their onset of activity, duration of effect, and potential for toxicity.

A DNA conformational alteration induced by a neighboring oligopurine tract on GAATTA enables nicking by EcoRI. The pseudo EcoRI site GAATTA in the U3 region of the long terminal repeat of human immunodeficiency virus, which is flanked by a 26-base pair oligopurine tract, is readily nicked by either EcoRI or RsrI. The strand-specific nick occurs predominantly between the G and A residues and is independent of negative supercoiling. Other GAATTA sites surrounded by random (non-oligopurine) sequences are not nicked by these restriction endonucleases. However, other types and lengths of oligopurine tracts are effective in inducing the nicking in neighboring GAATTA sites. Hence, we propose that the flanking oligopurine tracts induce an altered DNA conformation on the GAATTA target site which may be similar to the transition state induced by EcoRI when binding to its canonical recognition site. Gel retardation analyses on restriction fragments containing the oligopurine-GAATTA-oligopurine sequences suggest the presence of helical axis distortions which are consistent with this interpretation.

"Quality of life" for patients with end-stage renal failure. The assessment of health status and quality of life among chronically ill patients is an area of current scientific interest. This paper considers the utility of a short but comprehensive instrument to assess the quality of life for end-stage renal failure patients. the Spitzer QL-Index was completed by 8 nurses for all patients in the Wellington region currently being treated with home hemodialysis (n = 58); hospital hemodialysis (n = 13); and continuous ambulatory peritoneal dialysis (n = 37). Results indicated that home hemodialysis patients achieve the highest quality of life in comparison to the other two treatment modalities. It is concluded that the QL-Index has some discriminative validity for this patient population, and its use may contribute to informed decision making by both patients and doctors.

Marginal adaptation of Class V restorations using different restorative techniques. This in vitro study compares the marginal adaptation of Class V restorations with margins located half in enamel and half in dentine, which were placed using different restorative techniques. Five operative procedures were evaluated both in saucer-shaped erosion lesions and in box-shaped cavities with bevels in enamel. The five procedures included a composite inlay technique using both the chemically and the light curing versions of a resin based composite cement, a bulk placement technique using a chemically curing composite resin, an incremental technique and an incremental technique combined with a built-up base, using a light curing composite resin. A combination of Gluma/Clearfil served as the dentinal adhesive. The micromorphology of the tooth/restoration interface was analysed before and after thermal cycling; the marginal seal was analysed after thermal cycling only. In the conventional cavities, the restorations showed less leakage, and micromorphologically a better, but statistically insignificant superior marginal adaptation. The inlay technique rendered the best marginal quality in both enamel and dentine before and after thermal cycling. Due to the unique curing characteristics of the chemically cured composite resin and cement resulting in a significantly reduced rigid contraction, the inlays cemented with the chemically curing cement and the restorations placed with the chemically curing composite resin were superior to their light cured counterparts. The built-up base yielding a reduction of the composite mass did not enhance marginal adaptation because of the partial replacement of the strong adhesion to dentine mediated by the Gluma/Clearfil combination by the weaker bond promoted by the etched glass ionomer cement.

Urovirulence determinants in Escherichia coli isolates causing first-episode and recurrent cystitis in women. To assess the prevalence of urovirulence determinants among Escherichia coli isolates from women with acute uncomplicated cystitis, 121 isolates from 87 women with first-episode or recurrent cystitis and 156 fecal isolates from 52 women without recent urinary tract infection were tested using DNA probes for P fimbriae, hemolysin, aerobactin, and diffuse adhesin and for expression of hemolysin and P and F adhesins. P fimbrial genotype (P = .002), hemolysin phenotype (P = .007), and the diffuse adhesin determinant (P = .03), but not aerobactin, were found more frequently in E. coli from women with acute cystitis, and expression of the F adhesin (41%) was more common than the P adhesin (24%; P = .001). E. coli isolates that caused cystitis in women using diaphragms had fewer virulence determinants than those from nonusers (P = .04), suggesting that diaphragm use may allow infection with less virulent E. coli.

Pachyonychia congenita: a clinical study of 12 cases and review of the literature. Twelve cases of pachyonychia congenita were reviewed. The mode of inheritance was autosomal dominant. The clinical features of these patients included thickened nails, hyperkeratosis of the palms and soles, thinning of hair or alopecia, painful bullae or ulcerations of the palms and soles, leukokeratosis oris, verrucous lesions of the extremities, hyperhidrosis, premature eruption of teeth, paronychial infections, epidermal cysts with milia, and corneal dyskeratosis at times associated with cataracts. Biopsy from the plantar lesions usually revealed marked hyperkeratosis, acanthosis, moderate hypergranulosis, and minimal dermal inflammatory infiltration. Treatment with keratolytic agents and lubricants is indicated to areas of palmar and plantar hyperkeratosis but usually produces only transient benefit. Squamous cell carcinoma developed in one of the patients over the site of chronic plantar ulcerations. Areas of chronic bullous formation or ulceration should be observed for possible skin malignancy.

Cytokines regulating human B cell growth and differentiation. Utilizing a model system of anti-CD3-stimulated T cells, we have identified a potent B cell differentiation factor (BCDF) in the supernatant of these cells. This factor, 446-BCDF, appears to act on SAC-activated B cells inducing a 10- to 100-fold increase in Ig secretion. 446-BCDF has an apparent MW of 32 kDa and a pI of 6.0. Its activity cannot be inhibited by an anti-IL-6 antiserum, and activity is enhanced after passage over an anti-IL-6 affinity column. 446-BCDF activity is detected in the 50 mM salt fraction eluted from a Mono Q column. This 50 mM fraction has the only activity detected after passage over an anti-IL-6 affinity column and migrates with an apparent pI of 6.0. Taken together these data suggest that 446-BCDF is a unique potent polyclonal human BCDF which may be a predominant factor regulating terminal B cell differentiation.

Macrophages in human sensory ganglia: an immunohistochemical and ultrastructural study. The paper describes the immunohistochemical and ultrastructural features of normal posterior root ganglia in a group of humans aged 1 day to 80 years and compares the findings with those seen in the ganglia of normal rats of various ages, some of which underwent permanent traumatic lesions of the sciatic nerve. In humans, cells with the immunohistochemical reactions of macrophages are present in small number at birth, most of them having an endoneurial position. Subsequently, their number increases and more of them are seen around neurons, where their processes intermingle with those of satellite cells. Ultrastructural studies confirm that, in addition to interstitial cells, a small number of cells in satellite position have features of mesenchymal cells. In this respect, human sensory ganglia differ from those of rodents and this difference may explain why no nodules of Nageotte can be found either in ageing animals or after a permanent damage to the nerve has produced considerable cell loss. Other features observed in human ganglia, but absent in rats, are multiple layers of satellite cells surrounding each neuron and desmosome-like structures between satellite cell processes. Previous studies describing maturation of the satellite-nerve cell complex in animals are confirmed. In addition, the present investigation shows that, in human ganglia, satellite cells acquire a more elaborate structure than in rodents. It is also suggested that mesenchymal cells may play a role in the trophism of nerve cells and their removal after irreversible damage.

[Various types of small intestine occlusion. Case contribution]. The Authors examine retrospectively all the cases of obstruction of the small bowel operated at the surgical department of the Verbania Hospital in the last twenty years. The records of 341 cases, 1.4% of the total amount of the surgical operations carried out in the same space of time, were retrospectively reviewed. The Authors consider the data relating to sex, age, interval between hospitalization and operation, surgical treatment, possible previous operations, post-operative stay in hospital and complications. Having found a rate of complications significantly higher in those cases of obstruction that have required the resection of one or more intestinal loops (in all 69 cases, among them 50 cases belong to the group of the adhesions and of the strangulation), the Authors conclude by underlining the importance of recognizing and treating in time the cases where there is an irreversible vascular suffering of the bowel.

Validity of single variables and composite indices for measuring disease activity in rheumatoid arthritis. There is no agreement as to which variable best mirrors disease activity in rheumatoid arthritis (RA) and no studies have been performed on the validity of disease activity variables. In this study the validity of 10 commonly used single variables and three composite indices was tested. All patients participated in a large follow up study in two clinics. The patients (n = 233) had classical or definite RA and a disease duration of less than one year at entry. The mean follow up time was 30 months; the follow up frequency was once every four weeks; 6011 records were used in the analysis. The validation criteria included correlations with the other variables (correlational validity), with the physical disability (criterion validity I), and with the radiographically determined damage of hands and feet (construct validity). The judgment of a group of rheumatologists in clinical practice was also used as a model of criterion validity (II). In this comparison the disease activity score and Mallya index showed the best validity. The best single variable was the number of swollen joints. The validity of most single variables was poor and these variables were not suitable as single endpoint measures in clinical trials.

[The body muscle compartment and its relationship to food absorption and blood chemistry during an extreme endurance performance]. The purpose of the study was to examine the changes of the muscle's fat-free compartment and its relation to the corresponding biochemical and nutritional parameters of 42 men and 13 women, the participants of an ultra long-distance run of 1000 km (20 days of daily running 50 km). The muscle-fractions initially increased, decreased in the middle phase, and remained stable for the rest of the run. Significant changes of the fat-free weight were registered from the 11th day on, the LBM decreasing until the middle of the distance; then the lean body mass enlarged. All the muscle-circumferences were reduced with the exception of the thigh, which grew, paralleling the CK/CKMB-concentrations, this phenomenon being due to the high mechanical stress of the lower extremities. The biochemical parameters exhibit a strain-related reaction of adaptation within the initial 6 days, the hormones and protein-concentration increasing in the beginning and falling from the third day on, uric acid and CK/CKMB-activity decreasing from the 6th day on. The consecutive parallel reduction of both uric acid, urea, and muscle measurements might be seen as a special endurance-related clearance-mechanism of potential toxicants. The negative relationship between the changes of muscle measurements and the cumulative protein intake and the catabolic constellation of the clinical-chemical values might suggest that the absolute protein intake of 1.7 g/kg body mass should be increased in order to diminish the loss of musculature during an ultra-long distance run.

Identification of UDP-glucose as an intermediate in the biosynthesis of the membrane-derived oligosaccharides of Escherichia coli. The membrane-derived oligosaccharides of Escherichia coli constitute a closely related family of oligosaccharides containing approximately 9 glucose units variously substituted with sn-glycero-1-phosphate and phosphoethanolamine residues derived from the head groups of membrane phospholipids, and also with succinate in O-ester linkage (Kennedy, E.P., Rumley, M.K., Schulman, H., and van Golder, L.M.G. (1976) J. Biol. Chem. 251, 4208-4213). Studies with mutant strains defective in the synthesis of various nucleoside diphosphate sugars have now revealed that UDP-glucose is an essential intermediate in the biosynthesis of these oligosaccharides. Mutants unable to synthesize UDP-glucose do not contain significant amounts of the membrane-derived oligosaccharides. In contrast, a strain unable to synthesize ADP-glucose, the glucosyl donor for glycogen synthesis in E. coli, contained normal amounts of the membrane-derived oligosaccharides, although with a somewhat different pattern of distribution of the various subspecies. In confirmation of these genetic studies, pulse-label isotope tracer studies have been carried out with glucose of high specific activity, under conditions in which UDP-glucose comprises a large fraction of the total radioactivity in the low molecular weight pool. Subsequent "chase" experiments clearly revealed the conversion of UDP-glucose to the higher molecular weight membrane-derived oligosaccharides.

Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection. Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Pregnancy-induced changes in the maximal physiological responses during swimming. The effect of pregnancy on peak O2 uptake (VO2 peak) during tethered swimming was evaluated in 10 women during their 25th and 35th wk of pregnancy, as well as 9-11 wk postpartum. The swim results were compared with cycle ergometry results obtained at similar times. The results indicated that exercise-induced maximal heart rates remained the same and were similar for the swim and cycle trials, approximately 184 +/- 4 beats/min. Cycling VO2 peak was not affected by pregnancy, averaging 1.94 +/- 0.11 l/min. Postpartum swim VO2 peak was similar to the cycle results; however, during pregnancy it was significantly lower than cycling VO2 peak (P less than 0.05; postpartum, 1.78 +/- 0.14 l/min; 25th wk, 1.64 +/- 0.12; 35th wk, 1.48 +/- 0.11). Hemoglobin concentrations and hematocrits were lower during pregnancy; however, changes in plasma volume (based on hematocrit and hemoglobin) were found to be significantly greater during cycling than during swimming and also greater during pregnancy for both modes of exercise. It was concluded that, unlike cycling, the VO2 peak of pregnant women during swimming is reduced. This reduction in VO2 peak was associated with a decreased peak ventilation (r = 0.864) but was not correlated to exercise-induced hemoconcentration (r = -0.29). Furthermore, pregnancy results in a greater-than-normal exercise-induced hemoconcentration, which may be related to pregnancy-induced changes in capillary dynamics.

The aetiology of intellectual disability in Western Australia: a community-based study. A register of intellectual disability is being established to assess the level and aetiology of intellectual disability in all children born and/or living in Western Australia. 1602 children aged between six and 16 years were identified who had IQs less than 70. 40 per cent had a definite genetic basis, 20 per cent an environmental cause and 40 per cent were of unknown aetiology. The insult was prenatal in 61 per cent, 10 per cent had a possible perinatal cause, 8 per cent were postnatal and for 21 per cent the timing could not be assessed. Approximately 20 per cent had concomitant cerebral palsy and 13 per cent were epileptic. A disparity was found between rural and urban areas, the prevalence being 9.9 and 6.5 per 1000 live births.

Characterization of monoclonal antibody 436 recognizing the Arg-Pro-Ala-Pro sequence of the polymorphic epithelial mucin (PEM) protein core in breast carcinoma cells. Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a M(r) of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphorylation of double-stranded DNAs by T4 polynucleotide kinase. The phosphorylation by T4 polynucleotide kinase of various double-stranded DNAs containing defined 5'-hydroxyl end group structures has been studied. Particular emphasis was placed on finding conditions that allow complete phosphorylation. The DNAs employed were homodeoxyoligonucleotides annealed on the corresponding homopolymers, DNA duplexes corresponding to parts of the genes for alanine yeast tRNA, and a suppressor tyrosine tRNA from Escherichia coli. The rate of phosphoylation of DNAs with 5'-hydroxyl groups in gaps was approximately ten times slower than for the corresponding single-stranded DNA. At low concentrations of ATP, 1 muM, incomplete phosphorylation was obtained, whereas with higher concentrations of ATP, 30 muM, complete phosphorylation was achieved. In the case of DNAs with 5'-hydroxyl groups at nicks approximately 30% phosphorylation could be detected using 30 muM ATP. A DNA containing protruding 5'-hydroxyl group ends was phosphorylated to completion using the same conditions as for single-stranded DNA, i.e., a ratio between the concentrations of ATP and 5'-hydroxyl groups of 5:1 and a concentration of ATP of approximately 1 muM. For a number of DNAs containing protruding 3'-hydroxyl group ends and one DNA containing even ends incomplete phosphorylation was found under similar conditions. For all these DNAs a plateau level was observed varying from 20 to 45% of complete phosphorylation. At 20 muM and higher ATP concentrations, the phosphorylation was complete also for these DNAs. With low concentrations of ATP a rapid production of inorganic phosphate was noted for all the latter DNAs. The apparent equilibrium constants for the forward and reverse reaction were determined for a number of different DNAs, and these data revealed that the plateau levels of phosphorylation obtained at low concentrations of ATP for DNAs with protruding 3'-hydroxyl group and even ends is not a true equilibrium resulting from the forward and reverse reaction. It is suggested that the plateau levels are due to formation of inactive enzyme-substrate and enzyme-product complexes. For all double-stranded DNAs tested, except DNAs containing protruding 5'-hydroxyl group ends, addition of KCl to the reaction mixture resulted in a drastic decrease in the rate of phosphorylation, as well as in the maximum level phosphorylated. Spermine, on the other hand, had little influence. Both of these agents have previously been shown to activate T4 polynucleotide kinase using single-stranded DNAs as substrates (Lillehaug, J.R., and Kleppe, K. (1975), Biochemistry 14, 1221). The inhibition of phosphorylation of double-stranded DNAs by salt might be the result of stabilization of the 5'-hydroxyl group regions of these DNAs.

Cardiovascular complications in renal failure. Cardiovascular diseases are a leading cause of death in end-stage renal disease (ESRD) largely as a result of the progressively increasing age of ESRD patients and the broad constellation of uremia-associated factors that can adversely affect cardiac function. Hypertension, one of the leading causes of renal failure, is a major culprit in this process, causing left ventricular hypertrophy, cardiac chamber dilation, increased left ventricular wall stress, redistribution of coronary blood flow, reduced coronary artery vasodilator reserve, ischemia, myocardial fibrosis, heart failure, and arrhythmias. In addition to impairing the coronary microcirculation, hypertension may contribute to the development of atherosclerotic coronary artery disease, particularly in the presence of the many lipid abnormalities observed in ESRD. These patients have reduced high-density lipoprotein cholesterol and increased plasma triglyceride concentrations, and there is a defect in cholesterol transport. Other abnormalities that may contribute to atherosclerotic coronary artery disease in ESRD are reduced high-density lipoprotein cholesterol synthesis and reduced activity of the reverse cholesterol pathway. Treatment with fibric acids, nicotinic acids, and lovastatin may be useful in lowering cholesterol and triglyceride concentrations in some of these patients. The incidence of coronary artery disease in ESRD populations is difficult to determine. About 25 to 30% of ESRD patients with angina have no evidence of significant coronary artery disease, and an undetermined number have silent coronary disease. The presence of resting electrocardiographic abnormalities caused by hypertension or conduction defects makes it difficult to accurately diagnosis coronary artery disease in ESRD populations by noninvasive methods, including exercise testing and thallium scintigraphy with or without the use of dipyridamole. Hypotension is a frequent complication of the dialytic process. Many factors have been implicated, including autonomic neuropathy. There is no consensus on the function of the efferent limb of the sympathetic nervous system. The afferent limb (arterial baroreflex function) is felt to be impaired. Further, there may be defects in the ability of the cardiovascular system to respond to sympathetic nerve activity. Most studies of autonomic function have used indirect measurements. Studies are underway that use techniques to assess sympathetic function directly. Such experiments with microneuropathy suggest greater skeletal sympathetic muscle discharge in uremic patients than in normal patients.

[Ventilation aerosol therapy (author's transl)]. Ventilation aerosol therapy (a combination of intermittent positive pressure artificial respiration with aerosol therapy) produces a mechanical support for the breathing, achieves an effective aerosol action and promotes expectoration. It makes possible an effective treatment of inflammatory and obstructive bronchopulmonary diseases. The expense of apparatus and personnel for this method of treatment can only become rational and more economical for the large number of outpatients and hospitalized patients by taking advantage of a special department. The functional areas of such a ventilation aerosol department should be: outpatient department for artificial respiration, bedside artificial respiration and aerosol, ward for ventilation aerosol therapy and ventilation aerosol therapy under supervision and intensive care.

[Dichlorphenamide treatment in acute glaucoma (author's transl)]. Dichlorphenamide as well as Diamox lowers intraocular pressure. For adequate treatment of acute glaucoma only 20% of commonly used Diamoxdosis is requested to reach comparable pressure release two hours later. After one hour control intraocular pressure of 60% from patients with Dichlorphenamide treatment was found below 40 mm Hg since in Diamoxgroup there were only 30% below 40 mm Hg. Different effects of Dichlorphenamide and Diamox after one hour use is demonstrated in respect of serum electrolytes and base excess as well. Essential side effects after a single dosis of 200 mg Dichlorphenamide or in combination with Diamox for acute glaucoma treatment could not be observed.

Modulation of fluoroaluminate-induced inositol phosphate formation by increases in tissue cyclic AMP content in bovine tracheal smooth muscle. 1. The effect of fluoroaluminate complexes (AlCl3 plus NaF) upon smooth muscle tone, [3H]-inositol phosphate accumulation and [3H]-cyclic AMP accumulation has been investigated in slices of bovine tracheal smooth muscle. 2. Fluoroaluminate (10 microM AlCl3 + various concentrations of NaF) elicited concentration-dependent contractions of bovine tracheal smooth muscle strips at concentrations of NaF in the range 1-10 mM. The resultant contractile response was reversed by isoprenaline (50 nM) and was preserved in calcium-free medium. 3. Fluoroaluminate stimulated [3H]-inositol phosphate formation at concentrations of NaF over 1 mM. The response to 20 mM NaF + 10 microM AlCl3 was 164 +/- 29% of the response to 1 mM histamine. Fluoroaluminate also increased the incorporation of [3H]-myo-inositol into membrane phospholipids. 4. Fluoroaluminate produced a small rise in [3H]-cyclic AMP levels (2.1 fold increase over basal with 20 mM NaF). The response to forskolin (1 microM, 8.6 fold over basal) was reduced by fluoroaluminate in a concentration-dependent manner, but still remained significantly (P less than 0.05) elevated over the response to fluoroaluminate alone. 5. The [3H]-inositol phosphate response to fluoroaluminate was inhibited by salbutamol (maximum inhibition 60%, IC50 = 0.08 microM), forskolin (1 microM, 46% inhibition) and isobutylmethylxanthine (1 mM, 73% inhibition). 6. These data suggest that inhibition of agonist-induced inositol phospholipid turnover by cyclic AMP in this tissue can occur at the post-receptor level.

Development of CCK-B antagonists. Our approach to design small molecule non-peptide analogues of the neuropeptide cholecystokinin (CCK) has led to the discovery of the CCK-B antagonist 'dipeptoids'. A representative member of this series of compounds, PD134308 [R-(R*,R*)]-4-[[2-[[3-(1H-Indol-3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbonyl]amino]propyl] amino]-1-phenylethyl]amino]-4-oxobutanoic acid has high affinity (Ki = 1.7 nM) and selectivity for the CCK-B receptor (CCK-A/B ratio is 2500:1), is well absorbed and shows robust anxiolytic properties in several anxiogenic models in a dose related manner by both s.c. and oral routes of administration over the dose range 0.1-30 mg/Kg. The rational design of these dipeptoids from CCK 26-33 has involved the identification of the non-contiguous dipeptide fragment of CCK, Boc-Trp-Phe-NH2 with low micromolar affinity in binding assays. This dipeptide has been systematically chemically modified at the N- and C-terminal to increase CCK-B binding affinity 10,000-fold. These modifications include replacement of the L-tryptophan moiety by the non-genetically coded D-alpha-methyltryptophan residue. The modifications also enhance the stability of the molecule towards enzymatic and acid degradation and increase overall lipophilicity compared with the peptide in order to facilitate penetration of the blood-brain barrier.

Alterations in cholecystokinin peptide and mRNA in actively epileptic human temporal cortical foci. The cholecystokinin (CCK) content of temporal cortex, obtained at neurosurgery from 22 patients with temporal lobe epilepsy, was measured by a specific radioimmunoassay. Tissue immunoreactivity was identified as authentic sulfated CCK-8 by reverse phase high performance liquid chromatography. Several samples were also analyzed by RNA blot hybridization for preproCCK mRNA. The CCK content of cortical tissue from which active epileptic spiking was recorded at the time of surgery (11 patients) was significantly decreased (20% lower) in comparison to tissue samples from a second group of 11 patients in whom the lateral temporal cortex was electrographically free of epileptiform spikes. These data suggest that the decrease may be due to continuous release of CCK as a result of abnormal neuronal firing within the focus. This hypothesis may also be consistent with our observation of a slight increase (67%) in preproCCK mRNA in the actively spiking group compared to the non-spiking cortical samples.

The effects of two levels of linguistic constraint on echolalia and generative language production in children with autism. The effects of specific types of adult antecedent utterances (high vs. low constraint) on the verbal behaviors produced by three subjects with autism were examined. Adult utterance types were differentiated in terms of the amount of control the adults exhibited in their verbal interactions with the subjects during a free play setting. Videotaped interactions were analyzed and coded according to a predetermined categorical system. The results of this investigation suggest that the level of linguistic constraint exerted on the child interactants during naturalistic play sessions affected their communicative output. The overall findings suggest that (a) adult high constraint utterances elicited more verbal utterances in general, as well as a majority of the subjects' echolalia; (b) adult low constraint utterances elicited more subject high constraint utterances; and (c) the degree of constraint of adult utterances did not appear to influence the mean lengths of subjects' utterances. The results are discussed in terms of their implications for educational interventions, and suggestions are made for future research concerning the dynamics of echolalia in interactive contexts.

The usefulness of serum thyroglobulin in the follow-up of differentiated thyroid carcinoma in children. Serum thyroglobulin has been measured serially in ten children aged 5-17 years presenting with differentiated thyroid carcinoma. At presentation 4 had intra-thyroidal disease, 3 had lymph node metastases, and 3 had lung metastases. During follow-up for a median of 37.0 months (range 21-108) 3 patients have been disease-free, 4 have had a local relapse, and 3 have had persistent disease. Seventy-seven separate serum thyroglobulin measurements have been performed; 36 on and 41 off thyroid replacement therapy. A level of thyroglobulin of less than 5 ng/ml was taken as indicative of absence of disease, and compared against combined clinical examination and 131I scanning. Overall sensitivity of thyroglobulin measurement was 36/37 (97%), and although specificity was 30/40 (75%), this rose to 30/32 (94%) if raised thyroglobulin levels noted within 3 months of 131I therapy in otherwise asymptomatic patients (n = 4) or in subjects with intact thyroid tissue (n = 4) were excluded. Concordance with clinical status was 30/31 (97%) in measurements taken on, and 31/32 (94%) in those taken off, thyroid replacement. These data indicate that thyroglobulin measurement is a sensitive and specific means of detecting residual, recurrent, and metastatic thyroid carcinoma in children.

Role of cholecystokinin in postprandial and vagally stimulated duodenal and gallbladder motility in dogs. This study was designed to determine the role of cholecystokinin (CCK) in postprandial motility pattern of the duodenum and gallbladder (GB) in conscious dogs provided with chronic duodenal electrodes for recording of myoelectric activity and GB fistulas for measurement of intraluminal pressure and volume of GB and to calculate the GB motility index (MI) and GB emptying rate. During naturally occurring activity front (phase III MMC) in the duodenum there was significant increase in the MI of GB accompanied by about 20-30% reduction in the GB volume. These changes in duodenal and GB motility pattern could be duplicated by i.v. motilin. Feeding abolished the appearance of spontaneous activity front in the duodenum and greatly increased motility of GB while reducing its volume. Administration of CCK receptor antagonists in fed dogs failed to affect the motility changes induced by meal in the duodenum but abolished these of the GB. Vagal cholinergic stimulation with insulin, 2DG or urecholine caused similar effects to that induced by food i.e. increased duodenal spike activity, abolished phase III of the MMC, decreased GB volume and increased GB motility. Pretreatment with CCK antagonists did not affect significantly duodenal spike activity or GB motility but significantly increased the GB volume. Atropine 125 micrograms/kg) blocked almost completely spontaneous activity front in the duodenum and accompanying alterations in the motility and volume of GB. We conclude that CCK contributes to the MMC related alterations in the GB motor activity and is essential in cholinergic stimulation induced of the GB emptying but not in vagally induced duodenal and GB motility.

In vitro assay for responsiveness of lymphocytes to transfer factor by a new leukocyte migration inhibitory test. Transfer factor (TF) causes nonimmune lymphocytes to produce leukocyte migration inhibitory factor (LMIF) in the presence of purified protein derivative (PPD). The activity of TF was measured by leukocyte migration inhibitory test (LMIT). The LMIT was a modification of the conventional agarose droplet method. To express the activity of LMIF quantitatively and simply, LMIF titer was introduced. The LMIF titer was obtained from the combination of two factors, LMIF dilution and cell migration diameter, and therefore this made the LMIT much more sensitive as compared to the conventional LMIT. The responsiveness of lymphocytes from acute lymphoblastic leukemia (ALL) and from cell-mediated immunodeficiency in children to TF was assayed by LMIT. In ALL, the lymphocyte responsiveness was poor in relapse but improved with remission. The responsiveness was remarkably well in 3 patients with cell-mediated immunodeficiency. This method appears useful for the in vitro evaluation of responsiveness of lymphocytes to TF.

Generation: a corporate-sponsored retiree health care program. Generation is a geriatric clinic program sponsored by Southern California Edison Company for the company's retirees and their dependents. This innovative program uses a multidisciplinary team approach, including a comprehensive health and psychosocial assessment, complete medication review, retiree advisors, health promotion programs, and case management services. In its pilot phase, Generation has served more than 175 Edison retirees and dependents aged 53-96. In addition to traditional medical care, participants receive aggressive intervention regarding polypharmacy problems, health education workshops, individual and group counseling, and access to community resources. Ongoing research seeks to evaluate the program's effectiveness in providing high-quality health care services while containing costs.

[A case of aspirin-induced asthma due to ketoprofen adhesive agent]. A 40-year-old woman who had been diagnosed as having aspirin-induced asthma was admitted with stridor. She had a history of surgery for sinusitis and nasal polyps, and severe asthmatic attack requiring mechanical ventilation after administration of puranoprofen (Niflan). On the second day of hospitalization, she used a ketoprofen adhesive agent (Miltax, 30 mg) for a stiff shoulder. Stridor developed five hours later, progressing to a severe asthmatic attack with loss of consciousness, requiring mechanical ventilation. The serum level of ketoprofen was very high (81.7 ng/ml); therefore, provocation challenge test was performed to confirm the possible relationship between the ketoprofen adhesive agent and asthmatic attack. After closed patching of the agent (15 mg) on her lower leg, stridor developed, and FEV1.0 and PFR decreased, in association with an increase of the serum level of ketoprofen to a maximum of 38.0 ng/ml. These results show that the topical application of a ketoprofen adhesive agent induced the asthmatic attack by transdermal absorption in this patient.

Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Ventricular tachyarrhythmias are the major clinical manifestation of arrhythmogenic right ventricular disease. Although antiarrhythmic therapy has been widely advocated, there is only limited information available on the efficacy of antiarrhythmic drugs in these patients. The short- and long-term efficacies of various antiarrhythmic agents were retrospectively and prospectively analyzed in 81 patients (mean age, 39 +/- 14 years; range, 16-68 years; 61.7% males) with arrhythmogenic right ventricular disease. In 42 patients with inducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were obtained: class Ia and Ib drugs (n = 18), 5.6%; class Ic drugs (n = 25), 12%; beta-blockers (n = 8), 0%; sotalol (n = 38), 68.4%; amiodarone (n = 13), 15.4%; verapamil (n = 5), 0%; and drug combinations (n = 26), 15.4%. Only one of the 10 patients not responding to sotalol was treated effectively by amiodarone, whereas the remaining nine patients proved to be drug refractory toward all other drugs tested (3.8 +/- 2.3 drugs, including amiodarone in five cases) and underwent nonpharmacological therapy. During a follow-up of 34 +/- 25 months, three of the 31 patients (9.7%) discharged on pharmacological therapy had nonfatal recurrences of ventricular tachycardia after 0.5, 51, and 63 months, respectively. In 39 patients with noninducible ventricular tachycardia during programmed ventricular stimulation, the following efficacy rates were observed: class Ia and Ib drugs (n = 16), 0%; class Ic agents (n = 23), 17.4%; beta-blockers (n = 7), 28.6%; sotalol (n = 35), 82.8%; amiodarone (n = 4), 25%; verapamil (n = 24), 50%; and drug combinations (n = 11), 9.1%. During a follow-up of 14 +/- 13 months, four of 33 patients (12.1%) discharged on antiarrhythmic drugs had nonfatal relapses of their clinical ventricular arrhythmia. Thus, in arrhythmogenic right ventricular disease, sotalol proved to be highly effective in patients with inducible as well as noninducible ventricular tachycardia. Patients with inducible ventricular tachycardia not responding to sotalol are likely to not respond to other antiarrhythmic drugs and should be considered for nonpharmacological therapy without further drug testing. Amiodarone did not prove to be more effective than sotalol and may not be an alternative because of frequent side effects during long-term therapy, especially in young patients. Verapamil and beta-blockers were effective in a considerable number of patients with noninducible ventricular tachycardia and may be a therapeutic alternative in this subgroup. Class I agents appear to be rarely effective in the treatment of both inducible and noninducible ventricular tachycardia in arrhythmogenic right ventricular disease.