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Identification of a high molecular weight trans-membrane protein in mouse L cells. We have developed a new method for identifying proteins which span the plasma membrane ("trans-membrane" proteins) of mammalian cells grown in tissue culture. The method involves labeling proteins exposed on the cell surface with 125I by the lactoperoxidase technique and then preparing sealed, "inside-out" membrane vesicles (phagosomes) from the labeled cells using the polystyrene latex bead procedure. These inside-out vesicles are then treated briefly with trypsin and analyzed by SDS-polyacrylamide gel electrophoresis for the presence of 125I-labeled protein species which were degraded by proteolytic attack. Such proteins must be exposed on both the outer and inner membrane surfaces and, therefore, they must pass through the lipid barrier. This method is a general one in the sense that it is suitable for use with a wide variety of cell types, and here we show how it has been employed to prove that a particular high molecular weight polypeptide, called band 1, spans the plasma membrane of mouse L cells. Further studies of the band 1 polypeptide have demonstrated that it is preferentially exposed on the L cell surface during G1 phase of the cell cycle. Progression of cells from G1 to S is accompanied by a marked decrease in the availability of band 1 to iodination and it remains unavailable until cells re-enter G1. It is suggested that the band 1 polypeptide may be functionally involved in the regulation of cell proliferation.

Longitudinal changes in bronchial hyperresponsiveness in asthmatic and previously asthmatic children. To determine if nonspecific bronchial hyperresponsiveness is present to the same degree in previously asthmatic children compared with currently asthmatic children, a longitudinal study was conducted. On the basis of a standardized respiratory questionnaire, 139 children from asthmatic families, between the ages of 6 and 21 years, were identified. Subjects had skin tests, a serum IgE level, and a methacholine challenge test. IgE and skin tests demonstrated atopy in both the previously and currently asthmatic children, which persisted over time. Bronchial hyperresponsiveness within the asthmatic children was not significantly different between visits. Previously asthmatic children did have significantly decreased airway hyperresponsiveness over time. Age did not affect the results of the bronchial hyperresponsiveness in the currently asthmatic children. Currently asthmatic children, however, were significantly more atopic when compared with previously asthmatic children at their initial evaluation. Currently asthmatic children were also more bronchial responsive and remained so over time. Bronchial hyperresponsiveness is persistent in children with current asthma symptoms.

Sites of action of the KCl-soluble protein in the stimulation of protein synthesis in sea urchin systems. The sites of action of the KCl-soluble protein (KSP) in the stimulation of amino acid incorporation were studied with cell-free systems from sea urchin embryos. The reduced form of KSP stimulated amino acid- and tRNA-dependent AMP exchange in the amino acid activation and initiation steps. Stimulation of the binding of phenylalanyl-tRNA (Phe-tRNA) to 40 S ribosomes by KSP was found; the reaction was considered to be the binding to the donor site of ribosomes, based on the results of puromycin treatment, so this stimulation is assumed to occur at the initiation step. All other steps of amino acid-dependent exchange of PPi and ATP as well as hydroxamate formation, amino acid acceptor activity of tRNA, the binding of aminoacyl-tRNA, mRNA, and synthetic polynucleotide to ribosomes, translocation and peptide bond formation, and the termination and release of peptides from ribosomes, were apparently insensitive to KSP. Cyclic variation was observed in the activities of amino acid- and tRNA-dependent AMP exchange with ATP and the binding of aminoacyl (acylated and nonacylated)t-RNA to ribosomes using 12,000 x g supernatant. The reduced form of KSP itself had AMP exhange activity in amino acid activation. The reaction involved was confirmed to be aminoacyl transfer from aminoacyl-AMP to tRNA. However, low activities were observed for the bindings of Phe-and acetylphenylalanyl (AcPhe)-tRNA to ribosomes. Small molecular SH-reagents reacted in a different way from reduced KSP both in the AMP exchange reaction and the binding of aminoacy1-tRNA to ribosomes.

Intestinal worm burden and serum cholesterol or lipid concentration in a Shipibo population (Peru). Paired samples of stool and serum of 32 members of the Shipibo tribe resident in the rain forest of the Peruvian lowlands were tested for worm egg count and serum lipid parameters, respectively. 90% of the stool samples tested were found to contain eggs or larvae of several worm species, most commonly 3 or 4 different species. Serum lipid levels were found to be relatively low, most probably due to a low proportion of dietary fat ranging from 16-31%. Statistical analysis showed a significant inverse correlation between worm egg excretion and HDL levels which was true for hookworm, strongyloides and trichuris, but not for ascaris. The mechanisms underlying the observed association between intestinal worm load and HDL reduction are not completely understood and may include reduced HDL synthesis in the gut wall due to inflammatory and/or toxic irritation.

Factors that determine the cost and performance of early identification protocols. In this paper, a simple model is used to examine the relation between important factors, such as prevalence of hearing loss, and protocol performance and cost. Protocol hit rate is determined primarily by the hit rate of the screening protocol and follow-up percentage, the percentage of infants who return for diagnostic testing. Many factors influence protocol cost. Not only does absolute cost change as certain model parameters are varied, but the relative cost of different protocols can change as well. The false alarm rate of the screening protocol and the follow-up percentage have the greatest impact on protocol cost.

Evaluation of topical ketoconazole in cutaneous leishmaniasis. The efficacy of topical ketoconazole in cutaneous leishmaniasis (CL) caused by L. major was assessed in an open trial. Ten patients with twenty two lesions of CL, confirmed by smear/or biopsy, were recruited into the study. Of the twenty two lesions treated, three increased in size and lesion characteristics worsened, ten showed no change but in nine there was some improvement in lesion characteristics. No lesion healed completely. No side effects were reported in nine. Topically applied ketoconazole is safe but does not significantly alter the course of CL. The differences in the results of systematically administered and topically applied ketoconazole may be due to differences in the pharmacokinetics of the drug when it is administered by different routes.

Insulin and the glucose-glucagon feedback mechanism in the duck. The relationship between insulin and the glucose-glucagon feedback mechanism was studied by testing the effectiveness of various routes, doses and timing of insulin administration prior to and during a glucose tolerance test in Peking ducks made transiently diabetic by subtotal pancreatectomy. Insulin injections or infusions given either before, or only during the glucose load, did not restore the A-cell response to glucose. Yet, if given both before and during the glucose test, in conditions which mimic the physiological basal insulin level and its variations (with, initially, intramuscular injections of 0.2 IU/kg and 8 mug/kg glucagon, every six hours, and then an intravenous injection of 3.6 mU/kg plus an infusion of 0.9 mU/kg/minute for one hour), the normal glucagon response to glucose was re-established. Insulin must therefore be present, both before and during glucose stimulation, for glucose to be effective as an A-cell suppressor.

[Is angiotensin II a growth factor?]. Angiotensin II is an octapeptide resulting from the enzymatic cascade of the renin-angiotensin system and involved in vasoconstriction and aldosterone secretion. The extensive use of converting enzyme inhibitors recently suggested that angiotensin II may have a specific action on growth of its target tissues. Cellular models confirm that angiotensin II is able to produce in vitro a cellular hypertrophy of many cell types. Nevertheless a controversy was developed on the real possibility for angiotensin II to act on cell division. Some cells, such as adrenocortical cells, present a clear induction of their division by angiotensin II, but contradictory results were obtained on vascular smooth muscle cells. The mechanism by which angiotensin II induces hypertrophy of its target tissues, is largely unknown but may involve a direct action on proto-oncogene synthesis, or an indirect action on growth factor secretion. The nature of the angiotensin II receptor involved in these mechanisms has to be identified.

Peritoneoscopy in the staging of 190 patients with small-cell anaplastic carcinoma of the lung with special reference to subtyping. Peritoneoscopy with liver biopsy was routinely done as a pretreatment staging procedure in 190 patients with small-cell anaplastic carcinoma of the lung. Subtyping of the patients according to the WHO classification included 28.3% with fusiform cell type (WHO II,1), 28.9% with polygonal cell type (WHO II,2), 41.5% with lymphocytelike cell type (WHO II,3) and 1.3% with mixed types (WHO II, 4). Liver metastases were found in 21% of the patients with adequate liver biopsy. In addition macroscopic signs of liver metastases were observed in 9%. No significant differences were observed among the histological subtypes. Liver function tests, such as alkaline phosphatase, LDH and GOT, were of little value in excluding liver metastases. On the other hand, 2 of 3 abnormal liver function tests were highly indicative of liver metastases. In patients with positive liver biopsy, 41% had liver metastases alone and 76% had no other evidence of distant metastatic disease if bone-marrow involvement identified with bone marrow examination is excluded as a staging procedure.

Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130). The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed.

Assessment of anterior pituitary function during the post-partum period. In order to assess anterior pituitary function during the puerperium, 20 women were studied by 14 intravenous LRH and 10 TRH stimulation tests within 2-10 days post-partum. The basal FSH level (150-340 ng/ml) was within the normal non-pregnant range for the follicular phase of the menstrual cycle (50-350 ng/ml) and did not increase after 100 mug of synthetic LRH. The TSH (3.3-8.8 muU/ml) was high and increased after 200 mug of synthetic TRH about twofold. Obstetrical parameters (e.g. milk excretion, pregnancy complication, type of delivery or the amount of bleeding during delivery) were not associated with significant changes in FSH or TSH levels or in the responses to TRH stimulation.

Increased mucosal permeability after intestinal ischemia-reperfusion injury is mediated by local tissue factors. Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis. The present study was undertaken to determine whether these changes are mediated by local or systemic factors. In 6-week-old weanling rats, the ileum was divided into two isolated loops with separate vascular supplies. The mesentery of the proximal loop was occluded for 30 minutes, following which the bowel was reperfused; permeability to 51Cr EDTA was then assessed in the distal loop 30 minutes after reperfusion. In control groups, the distal loop was subjected to 30-minute IRI ("positive" control) or 30-minute sham operation ("negative" control). Permeability in the distal loop was increased only with IRI to the distal bowel (15.4 +/- 3 counts/min/standard), and not with IRI to the proximal bowel (5.1 +/- 1) or with sham operation (8.5 +/- 2). To determine whether a mild "priming" injury might be necessary for systemic factors to have an effect, the distal loop was subjected to 2-minute IRI and the proximal to 30-minute IRI or sham. Permeability was not increased in the distal loop in either of these groups (5.7 +/- 1 and 7.8 +/- 2, respectively). Thirty-minute IRI in the proximal loop did not increase permeability in the distal loop, with or without a priming injury. Only direct IRI in the distal loop resulted in a significant increase in permeability. We conclude that the permeability changes in this model are mediated through local tissue effects, rather than by systemic factors.

Enhanced affinity of opiate receptors for naloxone in striatal slices of morphine-dependent mice. Slices of corpus striatum were allowed to accumulate 3H-morphine and then they were placed in a small chamber and superfused with Krebs-Ringer bicarbonate solution. 100 to 1 pM of naloxone caused an immediate increase in the release of morphine from the slices when it was placed in the superfusion fluid at 0, 5 or 15 min after the the start of the superfusion. Slices from morphine-dependent mice were more sensitive to the naloxone-induced release of morphine than those of control mice. The data suggest that the affinity of the opiate receptors in the corpus straitum for naloxone is increased in morphine-dependent mice.

Verbal aggression by parents and psychosocial problems of children. Analyses of data on a nationally representative sample of 3,346 American parents with a child under 18 living at home found that 63% reported one or more instances of verbal aggression, such as swearing and insulting the child. Children who experienced frequent verbal aggression from parents (as measured by the Conflict Tactic Scales) exhibited higher rates of physical aggression, delinquency, and interpersonal problems than other children. This relationship is robust since it applies to preschool-, elementary school-, and high school-age children, to both boys and girls, and to children who were also physically punished as well as those who were not. Children who experienced both verbal aggression and severe physical violence exhibited the highest rates of aggression, delinquency, and interpersonal problems.

The capacity for arylsulfatase synthesis in synchronous and synchronized cultures of Chlamydomonas reinhardti. The green algae Chlamydomonas reinhardti synthesizes arylsulfatase (arylsulfate sulfohydrolase EC 3.1.6.1) by derepression when the concentration of SO4-2-minus in the growth medium is less than about 5-10-minus 5 M. The following observations indicate that the arylsulfatase enzyme is stable while its mRNA was unstable: (1) The increase in enzyme activity stopped and remained constant after addition of cycloheximide to derepressed cells. (2) After readdition of SO4-2-minus the increase in enzyme activity continued at a lower rate whereafter it remained constant. (3) No decay of radioactivity was observed after readdition of SO4 2-minus in labelled enzyme protein isolated from pulse-labelled --S cells. The maximum rate of arylsulfatase synthesis. Measurements of this capacity in cells taken at different developmental stages from a selection synchronous and from a light-dark synchronized culture showed that: (1) Arylsulfatase was derepressible at all stages of the life cycle. (2) The same periodic capacity patterns were found, both with the synchronized and the synchronous cells. Furthermore, the rate of accummulation of RNA and protein changed in the same periodic manner during the life cycle as did the enzyme capacity.

The contributions of interpersonal conflict to chronic pain in the presence or absence of organic pathology. This study investigated the influences of social support and interpersonal conflict on chronic pain in patients with arthritis or with myofascial disorders. Measures of social support, conflict, and pain were drawn from subscales of the McGill Pain Questionnaire, the Multidimensional Pain Inventory, the Family Environment Scale, and the Interpersonal Relationship Inventory. Patients with myofascial disorders reported significantly worse pain (sensory and affective), higher depression scores, more interpersonal conflict, and less support from others than patients with arthritis, but did not differ from them on personality traits. Also, the contributions of conflict to pain were found to depend on the nature of the chronic disorder and on the source of the conflict, i.e., significant other, family, or social network members. For patients with arthritis, less intense pain (sensory and affective) was associated with higher family conflict. Less intense sensory pain in arthritis was also associated with more punishing responses from the significant other to pain. For patients with myofascial disorders, more intense affective pain was associated with higher social network conflict. Social support did not significantly contribute to pain for either group. Thus, chronic painful disorders may differ on the influences that social relationships have on pain. The implications of these differences for treatment are discussed.

A local outbreak of paralytic rabies in Surinam children. A rapidly fatal encephalomyelitis, which was in most cases characterized by ascending paralysis, developed in seven children of the age of 3 to 10 years in a bushnegro village in the interior of Surinam. Rabies virus was recovered from the central nervous system of three autopsied children. Although the source of infection has not been detected, there is an indication that, at least in some cases, the disease has been transmitted by rat-bite rather than by vampire bats. During the same period a few cases of minor febrile illness occurred in the same community. Since virological and serological evidence of a wide-spread distribution of Coxsackie A virus type 4 was obtained, the latter illness may presumably be attributed to this virus.

[Comparison of the pA2 of various beta blocking agents]. The drug industry is now putting out specific beta 1 or beta 2 beta-blocking agents. The pA2 of various beta-blocking agents were determined on isolated organs-guinea pig atrium and trachea: practolol and acebutolol were considered as specific beta-1 inhibitors; butoxamine was a specific beta-2 inhibitor, while pindolol, oxprenolol, propranolol and alprenolol were specificity free. The pA2 quantifies the action exerted by an inhibitor. Cardioselectivity is expressed by the pA2 left atrium/pA2 trachea ratio. It exceeds 1 000 for practolol, it equals 30 for acebutolol, and is very slight for butoxamine. The pA2 therefore gives a good idea of the potential of the various drugs on the animal's isolated organ. However, these data cannot safely be extrapolated to man. Hence the necessity of conducting clinical pharmacological studies.

Nucleus-driven mutations of human mitochondrial DNA. Neuromuscular disorders due to abnormalities of mitochondrial energy supply have become an important area of human pathology. In particular, lesions of the mitochondrial genome (mtDNA), a small extra-nuclear chromosome which encodes 13 subunits of the respiratory chain complexes, are responsible for a steadily increasing number of neuromuscular syndromes. In addition to sporadic or maternally-inherited mutations, either qualitative or quantitative abnormalities of mtDNA can be transmitted as Mendelian traits, leading to well-defined mitochondrial encephalomyopathies. The latter are presumably caused by mutations in still unknown nucleus-encoded genes which deleteriously interact with the mitochondrial genome. These observations are of importance from both clinical and theoretical points of view, because they are the first examples of diseases produced by abnormalities of the nuclear control over mitochondrial biogenesis.

Expression of genes coding for pS2, c-erbB2, estrogen receptor and the H23 breast tumor-associated antigen. A comparative analysis in breast cancer. Expression of the gene coding for a new breast tumor-associated antigen, H23, was compared to expression of genes coding for pS2, c-erbB2 and estrogen receptor (ER). Comparison involved mRNA expression in normal and malignant breast tissues as well as in non-breast tumors. Results obtained by RNA dot blot and Northern hybridizations showed that expression of the H23 antigen coding gene is a discriminatory marker in human breast cancer. It is expressed in 92% of breast tumors whereas 69%, 62% and 56% of breast tumors demonstrate significant mRNA levels of c-erbB2, ER and pS2, respectively. Non-malignant or normal breast tissue expresses much lower levels of the H23 antigen mRNA. From the comparative analysis presented here it is concluded that the gene coding for H23 antigen furnishes a most useful marker for human breast cancer.

Decreased mitochondrial gene expression in isolated islets of rats injected neonatally with streptozotocin. The aim of the present study was to evaluate the possible role of the expression of the mitochondrial genome for the regulation of insulin production in the pancreatic Beta cell. For this purpose, islets of Langerhans were isolated from adult control rats and rats injected neonatally with streptozotocin and the islet contents of specific mitochondrial DNAs and RNAs together with nuclear-encoded RNAs were determined. The contents of mitochondrial cytochrome b mRNA, the mitochondrial 12 S rRNA and insulin mRNA were all 30-40% lower in islets isolated from the streptozotocin-treated rats as compared to islets from control rats. In contrast, the nuclear mRNA coding for the mitochondrial adenine nucleotide translocator was not decreased in the streptozotocin-treated rats. Contents of mitochondrial DNA, as assessed by the Southern blotting technique, were markedly decreased in the streptozotocin islets. Sequence analysis of mitochondrial DNA from streptozotocin islets and control islets however, did not reveal any differences in nucleotide sequences. In control islets the contents of mitochondrial cytochrome b mRNA increased in response to a high glucose concentration during a 4-h incubation period. Serum deprivation or the addition of theophylline or 4-phorbol 12-myristate 13-acetate failed to affect the cytochrome b mRNA contents in vitro. It is concluded that islets of streptozotocin-treated rats contain low contents of mitochondrial DNA and RNA. Since a lower mitochondrial RNA content may result in a diminished oxidative capacity, it is conceivable that a deficiency of this messenger may contribute to the development of insulin deficiency.

Transbronchial biopsy via flexible fiberoptic bronchoscope; results in 164 patients. The diagnostic accuracy and complication rate of transbronchial forceps lung biopsy combined with bronchial brushing were analyzed in 164 consecutive patients, of whom 95 had nonmalignant disease and 51 had malignant disease. Eighteen patients with abnormal chest radiographs had normal transbronchial forceps lung biopsies and no established diagnosis. Satisfactory specimens were obtained in 153 patients (93 per cent), with diagnositc accuracies of 62, 64, and 67 per cent, respectively, in infectious, interstitial, and malignant lung disease. The over-all diagnostic accuracy was 57 per cent. Seven patients were diagnosed as having metastatic carcinoma to the lung by transbronchial forceps lung biopsy, but brush biopsy was psoitive in only 3. Of the 23 patients with primary lung carcinoma diagnosed by transbronchial forceps lung biopsy, 21 had positive brush biopsies. An additional 3 patients with bronchogenic carcinoma, however, were diagnosed only by brush biopsy. Fluoroscopy was essential for accurate positioning of the biopsy instrument. Increased risk factors were present in 83 patients (51 per cent), among whom the immunosuppressed group presented special problems. Significant bleeding in 15 patients (9 per cent) was controlled by conservative management. Pneumothorax occurred in 7 patients (4 per cent). There were no deaths. Transbronchial forceps lung biopsy in experienced hands is safe and well tolerated. The physician, nevertheless, must be prepared to handle major complications, especially bleeding. The procedure has a resonable diagnostic yield in high-risk patients who have a variety of lung lesions.

Angiography in the diagnosis and management of extracranial vascular lesions of the head and neck. The angiographic features of various lesions of the head and neck are presented. Angiographically, cavernous hemangiomas display large venous lakes with calcified phleboliths. Arteriovenous malformations reveal massive tumor stain with well delineated feeding vessels from multiple systems. Chemodectomas and juvenile nasopharyngeal angiofibromas are clearly vascular with homogenous tumor staining in the capillary phase. Angiography of cavernous hemangioma, AVM, chemodectoma, and angiofibroma is diagnostic and may preclude the need for tissue biopsy. Angiographically neurilemmomas are less vascular with non-homogenous tumor stain. Carcinomas are typically avascular. The use and benefits of arterial embolization in the management of these lesions is presented.

Exercise performance after septal myotomy and myectomy in patients with obstructive hypertrophic cardiomyopathy. The effect of left ventriculomyotomy and myectomy on exercise capacity and cardiac function in patients with obstructive hypertrophic cardiomyopathy has not previously been determined. In this study, 29 patients were evaluated during graded treadmill exercise before and after operation. Postoperatively, 27 of 29 patients reported symptomatic improvement and had greatly reduced left ventricular outflow gradient. Twenty-five of 28 patients (89 percent) attained higher exercise levels after operation, and this was accompanied by an increase in total body oxygen consumption from 16 to 21 ml/min per kg (P less than 0.005). A significant increase in cardiac index during maximal exercise also accompanied this improved exercise performance (5.0 to 5.7 liters/min per m2, P less than 0.05). The increase in maximal cardiac index was associated with greater desaturation of mixed venous blood (34 to 24 percent, P less than 0.02) in patients with preoperative angina. At a given level of mixed venous oxygen saturation (30 percent), overall mean cardiac index was higher postoperatively (4.6 to 5.2 liters/min per m2, P less than 0.05). These results suggest that, although several mechanisms probably contribute to symptomatic improvement after myotomy and myectomy, enhanced cardiac performance plays an important role in the majority of patients.

Endogenous ultradian rhythms in rats exposed to prolonged continuous light. Circadian rhythms of locomotor activity, body temperature, and plasma corticosterone were determined simultaneously in individual rats that were exposed to 200 lx continuous light for over 3 mo. Free-running circadian rhythms of locomotor activity persisted for about 2 mo under continuous light and then the rhythms gradually decomposed. After 3 mo of exposure, circadian rhythms disappeared and activity bursts of 1- to 2-h duration manifested themselves several times during a 24-h period. Body temperature also exhibited several bursts of fluctuation and these bursts were closely correlated in their temporal sequence with those of locomotor activity. A least-squares spectrum analysis revealed that the burst had regular 4- to 6-h periods. Plasma corticosterone, determined by serial sampling at 2-h intervals from individual rats, also exhibited several secretion episodes in a day. These episodic secretions synchronized with bursts of locomotor activity. These results suggest that the ultradian component, manifested under prolonged continuous light, is a fundamental unit of the circadian rhythm and an oscillator for the ultradian rhythm is common to the three functions examined.

[The detection of neutrophilic myeloperoxidase in the skeletal muscles of rats after muscle activity]. Rat muscle infiltration by neutrophils after muscle activity (MA) was investigated on myeloperoxidase (MPO) concentration. MPO distribution in muscle subcellular fractions was also studied. Increase of MPO concentration in skeletal muscles was discovered after MA. Its maximum was determined within 1-5 days of the rest. This fact can be considered as an evidence of neutrophil influx in muscle tissue. The electroral MPO concentration increase in plasmalemma membrane fraction after MA was shown. In vitro MPO was able to catalyze 125I inclusion in membrane material. These results give a possibility to propose that neutrophil MPO can have a certain significance in muscle tissue damage by haloid joining to plasmalemma proteins.

The length of pregnancy: an echographic reappraisal. A study of 998 pregnant women was conducted to estimate the random errors in dating pregnancy by menstrual history and by ultrasound measurements of the fetus (crown-rump length or biparietal diameter before 20 weeks, menstrual age) as well as the biological variability of pregnancy length. The latter was found to be 7.74 days. The random errors made when dating pregnancy by menstrual history and by ultrasound measurements were 7.16 days and 4.26 days, respectively. (All variabilities are expressed as standard deviations). The differences between the two methods were mainly attributable to some large errors occurring when dating pregnancy on the basis of menstrual history. Differences between methods of more than 10 days were observed in about 10% of our population. When the two methods were used on the same patients to define a pregnancy as preterm, at term, or postterm, discrepancies were found in about 7% of cases.

Hepatic cytochrome P-4503A (CYP3A) activity in the elderly. Elderly patients exhibit decreased clearance of multiple drugs biotransformed by the hepatic cytochromes P-450. The cytochromes P-450 are a superfamily of enzymes, which comprise a central component of phase I drug metabolism. Distinct isoforms metabolize specific drugs. In human liver microsomes, the glucocorticoid-inducible cytochrome P-450IIIA, CYP3A, catalyzes the N-demethylation of erythromycin. To examine the activity of hepatic CYP3A in elderly males and females, erythromycin N-demethylation was examined, as reflected by the recently described [14C]erythromycin breath test in 24 healthy volunteers, age 70-88. The [14C]erythromycin breath test was measured in normal elderly males and females to: (a) determine persistence of the gender-related dimorphism (evident in younger subjects) of CYP3A activity in the elderly population, (b) examine the effect of % ideal body weight, age, diet, and medication use on the activity of human hepatic CYP3A, and (c) compare breath test results obtained in normal geriatric volunteers with published results obtained in younger subjects, to determine aging-related alterations in CYP3A enzyme activity. Erythromycin N-demethylation varied fivefold among these patients. Similar to earlier studies examining erythromycin N-demethylation in younger subjects, CYP3A activity was found to vary with gender in the geriatric cohort. [14C]Erythromycin N-demethylation at 60 min was 3.14% +/- 0.75 (n = 13) in females and 2.15% +/- 0.77 (n = 11) in males (P = 0.005). In evaluating the role of % ideal body weight and % dietary fat using multivariable linear regression analyses, [14C]erythromycin N-demethylation, was found to decline significantly as % ideal body weight increased (P = 0.001). This was not confounded by gender. [14C]Erythromycin N-demethylation was not related to dietary fat intake (P less than 0.13). [14C]Erythromycin N-demethylation in the elderly volunteers was similar to values reported for subjects aged 20-60. Performance of a new non-invasive test of the human hepatic glucocorticoid-inducible CYP3A in a geriatric cohort suggests that: (a) the gender-related heterogeneity in function of the glucocorticoid inducible human CYP3A persists during normal aging, (b) that the activity of CYP3A may decrease in obesity, and (c) that the activity of CYP3A is stable throughout normal ageing.

Neonatal morphometry. Relation to obstetric, pediatric, and menstrual estimates of gestational age. To determine gestational age-dependent neonatal morphometrics based on last menstrual periods (LMPs), Ballard examinations, and obstetric estimates of gestational age. Cross-sectional survey of 38,818 live-born neonates at a tertiary care center in Detroit, Mich. Consecutive sample of all viable, structurally normal, singleton neonates delivered at Hutzel Hospital from 1984 through 1991. Neonatal weights, lengths, and head circumferences were recorded at birth. Gestational age-dependent morphometrics were based solely on LMPs and compared with those based on obstetric estimates (using LMPs corrected by fetal ultrasound). Ballard examination had an 85.4% concurrence (within 14 days) with obstetric estimates of gestational age, but only a 69.9% (P less than .0001) agreement with LMP. Dating only by LMP significantly overestimated the prevalence of prematurity (odds ratio [OR], 1.3; 99% confidence interval [CI], 1.3 to 1.4) and postmaturity (OR, 5.0; 99% CI, 4.6 to 5.4), distorting apparent growth patterns, especially for preterm neonates. In contrast to previous studies based solely on LMPs, morphometric measurements increased beyond 40 weeks when dated by obstetric estimates. Gestational age-dependent neonatal morphometrics should not be based solely on LMPs.

Method for determination and element analysis of particulate contamination in injectable solutions. A method for sampling and evaluating the chemical and physical composition of particles in injectable solutions was developed. The technique facilitates detection of the particles' sources and possible medical hazards. Particles exceeding 0.2 mum are collected on a membrane filter sized for direct application in a scanning electron microscope (SEM). The sampling device shortens the distance between filter and solution and minimizes contamination from the filter holder. Following coating of the membrane filter with gold, the particles are counted by screening at a magnification of 5,000 x in the SEM. Both unused membrane filters and filters through which a solution of 0.9% sodium chloride had been passed were analyzed. X-ray analysis of particles on the clean filter revealed silicon, aluminum (artifact from the stud) and calcium. X-ray analysis of the filter after passage of 1 liter normal saline revealed chromium, copper, iron, magnesium, manganese, aluminum (from study), calcium chlorine, sodium and silicon. Recommendations for standard procedures for particle detection in large-volume injectables are given.

Natural history of autonomic neuropathy in chronic liver disease. To determine the natural history of autonomic neuropathy in chronic liver disease we used standard cardiovascular autonomic tests to evaluate prospectively 60 patients (33 male, 27 female) with initially well-preserved hepatic function. On initial testing, 27 patients (45%; median [range] age 56 [32-67] years) had vagal neuropathy. Autonomic dysfunction was equally common in patients with alcohol-related and nonalcoholic-related liver disease. The cumulative 4-year mortality rate in patients with vagal neuropathy was 30% compared with 6% in those with normal autonomic function. Multiple logistic regression analysis showed that presence of vagal neuropathy and severity of hepatic damage were independent predictors of mortality. Serial testing showed that whereas disease progression occurred in some patients, in others mild abnormalities in autonomic function were reversible. Vagal dysfunction is common in well-compensated chronic liver disease and its presence identifies a subgroup of patients with a substantially worse outlook.

Aromatization of androgens by human abdominal and breast fat tissue. The ability of human abdominal, breast and axillary fat to convert androgens into estrogens was investigated by incubating labeled substrates in the presence of NADPH with a variety of cell preparations. The incubation products were subjected to phenolic partition, paper chromatography, methyl-ether formation, repeat chromatography and crystallization with cold carrier reference standards to constant specific activity. Androstenedione was converted to estrone and, to a lesser extent, to 17beta-estradiol by crude homogenates, minces, fat-free particulate fractions (1,000-100,000 time g) and isolated fat cells obtained from abdominal, breast or axillary fat. Testosterone was found to be aromatized as actively as androstenedione, but inthis case more 17 beta-estrodiol was formed than estrone. 19-Hydroxyandrostenedione-2 also served as substrate, givingresults similar to those obtained with androstenedione. Fat tissue obtained from cancerous breasts was found to be as active as normal breast fat (1-4 pg/g fat/90 min) and within the range found for abdominal fat (1-27 pg/g fat/90 min). In each case in which axillary fat was compared to breast fat from the same subject, the activity of the axillary fat was 5 to 10 times higher. The results indicate a possible role of adipose tissue as a significant extra-gonadal source of estrogens.

Insulin alters the target size of the peripheral cyclic AMP phosphodiesterase but not the integral cyclic GMP-stimulated cyclic AMP phosphodiesterase in liver plasma membranes. Radiation inactivation of the two high affinity cyclic AMP phosphodiesterases (PDE) found in liver plasma membranes afforded an estimation of their molecular target sizes in situ. The activity of the peripheral plasma membrane PDE decayed as a single exponential with a target size corresponding to a monomer of circa 54 kDa. The integral, cyclic GMP-stimulated PDE decayed as a dimer of circa 125 kDa. Preincubation of plasma membranes with insulin (10nM), prior to irradiation, caused the target size of only the peripheral plasma membrane PDE to increase. We suggest that insulin addition causes the peripheral plasma membrane PDE to alter its coupling to an integral plasma membrane protein with a target size of circa 90 kDa.

[Echocardiographic size of the left atrium and pulmonary "capillary" pressure in different cardiopathies]. In order to investigate the relationship between left atrial pressure and volume, left atrial echograms and mean pulmonary wedge pressure were obtained on 64 patients with various cardiac diseases. A statistically significant relationship was found in the whole group (r = 0.67, p < 0.01), but there was a considerable degree of dispersion around the regression line. A good correlation was present in 6 patients with hypertrophic cardiomyopathy (r = 0.97, p < 0.01) and in 13 patients with long standing mitral valve disease (r = 0.85, p < 0.01). There was no correlation in coronary artery disease patients.

In vitro activation of adenylate cyclase by parathyroid hormone and calcitonin during normal and hydrocortisone-induced cleft palate development in the golden hamster. An adenylate cyclase highly responsive to stimulation by parathyroid hormone (PTH) and calcitonin (CT) in vitro was observed at certain times during normal prenatal development of the maxillary-palatal process complex in the golden hamster. Responses of the enzyme to these hormones were barely detectible at the earliest stage examined (day 10/20). The enzyme became extremely sensitive to activation by either hormone during the time of rapid growth of the palatal processes (day 11/20) and during fusion between the palatal processes (day 12/20). Thereafter, responses were greatly diminished and little or no activation of adenylate cyclase was observed until birth. Adenylate cyclase from fetuses in which clefts of the secondary palate were induced by maternal treatment with hydrocortisone (50 mg) on day 11/3 also displayed an enhanced sensitivity to PTH and CT on day 11/20, but the sensitivity of the enzyme was greatly decreased from that in normal animals during the normal time of palatal fusion (day 12/20) and was barely detectible or absent at the remaining time periods studied (days 13/20 and 14/20). Addition of hydrocortisone to the incubation mixture, either separately or in combination with PTH or CT, did not remarkably affect the response of adenylate cyclase to these hormones. Moreover, the appearance of the adenylate cyclase sensitive to hormonal activation did not result from changes in phosphodiesterase activity during palatal maturation.

Savings obtained by CA-125 measurements during therapy for ovarian carcinoma. The North Thames Ovary Group. The value of serial CA-125 measurements for predicting progression of ovarian carcinoma during therapy was calculated in 71 patients. The optimal algorithm that defined disease progression by CA-125 levels was either two values above 100 U/ml which had decreased by less than 50% over a minimum of 56 days, or a rise of 25% between successive samples plus a confirmatory sample. Of 13 patients with progressive disease according to the CA-125 criteria, 12 developed clinical evidence of progression within 12 months; predictions were false positive in 1, true negative in 50 and false negative in 8. Retrospective analysis showed that therapy and investigations costing 7979 pounds could have been avoided, if CA-125 assays costing 5470 pounds had been acted upon. The efficacy of the CA-125 algorithm is being independently verified to confirm that monthly CA-125 measurements whilst on treatment combine cost-effectiveness with a decrease in unpleasant interventions.

[Malaria tropica in HIV infection]. This is a case report of a 24 year-old woman who is HIV-infected since three years (stage III B, CDC). She developed malaria tropica during her touristic stay in the Cameroons, Africa. No clinical complications were detectable even though she had a high parasitemia of 18% blood cells infected with Plasmodium falciparum. After quinine therapy defervescence occurred and blood smears were continuously free of malaria parasites. P. falciparum infection may increase HIV-related immunosuppression which favours the earlier occurrence of AIDS indicative opportunistic infections. Malaria in combination with HIV-infection can lead to a higher parasitemia; this does not necessarily lead to a higher rate of complications.

Fluid secretion by the malpighian tubules of the tsetse fly Glossina morsitans: the effects of ouabain, ethacrynic acid and amiloride. The effects of three inhibitors of sodium transport on the secretion of fluid by the Malpighian tubules of Glossina morsitans have been observed. The cardiac glycoside, ouabain, affects neither the rate of secretion nor the sodium concentration of the fluid secreted when isolated tubules are bathed by solutions containing a range of sodium and potassium concentrations. Secretion is inhibited, however, by ethacrynic acid and amiloride. The results confirm that fluid secretion by the Malpighian tubules of this insect is dependent on the active transport of sodium ions and show that Na+/k+ exchange pumps are not involved in this process.

Nucleotide and deduced amino acid sequence of the nonstructural phosphoprotein, NS2, of bluetongue virus serotype 17: comparison to two isolates of serotype 10. The nucleotide sequence of bluetongue virus (BTV) serotype 17 segment 8 from North America (NA) coding for the nonstructural phosphoprotein, NS2, was determined. This segment contains 1125 base pairs and codes for a protein of 40,581 daltons containing 354 amino acids with a net charge of -8.5 at pH 7.0. The carboxyl terminal portion of the protein is very hydrophilic and has a high degree of potential alpha-helix. Serine is the major, if not the exclusive, phosphorylated amino acid residue and ten of the twenty serine residues present in NS2 are found in consensus phosphorylation sites. Comparison of the nucleotide sequence of BTV-17NA segment 8 with the sequence of BTV-10NA and BTV-10 South Africa (SA) revealed a greater degree of homology between different serotypes within the same geographical area, i.e., 17NA and 10NA, than between isolates of the same serotype located in different areas, i.e., 10NA and 10SA. The same homology relationship as above was found at the amino acid level.

Studies on the structure and regulation of the human hepatic interleukin-6 receptor. Affinity cross-linking of 125I-labeled recombinant human interleukin-6 (IL-6) to human hepatoma cells (HepG2) allowed the detection of three IL-6-containing complexes with molecular masses of 100 kDa, 120 kDa and 200 kDa. Treatment of HepG2 cells with dexamethasone led to a time- and dose-dependent up-regulation of IL-6-receptor mRNA levels. By the use of cross-linking this effect was also seen at the protein level, where all three IL-6-binding complexes increased upon incubation of HepG2 cells with dexamethasone. Under conditions of IL-6-receptor up-regulation by dexamethasone, gamma-fibrinogen mRNA induction by IL-6 is stronger and occurs earlier than without dexamethasone. We propose therefore that the expression of the IL-6 receptor might be a rate-limiting step in acute-phase-protein induction.

Ultrastructural detection of lectin receptors by cytochemical affinity reaction using mannan-iron complex. A two-step affinity reaction is described for electron microscopic demonstration of the Concanavalin A as well as the Lens culinaris lectin receptors by means of the yeast mannan-iron complex. First the tissue was incubated in the lectin. Afterwards the incubation in the yeast mannan-iron complex was performed and reaction takes place between the still free second sugar binding site of membrane bound lectin molecules and the polysaccharides. This membrane receptor-lectin-polysaccharide complex is revealed by the electron dense iron core of the yeast mannan-iron complex. The specificity of the reactions could be demonstrated by addition of the hapten or by incubation in the yeast mannan-iron complex only. The proposed technique has proved useful for demonstration of lectin receptors in the small intestine.

Ribosomal RNA gene restriction fragment diversity amongst Lior biotypes and Penner serotypes of Campylobacter jejuni and Campylobacter coli. Diversity based on ribosomal RNA gene-restriction endonuclease digest patterns was detected amongst 42 strains of Campylobacter jejuni and 18 strains of C. coli including representatives of 53 different Penner serotypes. HaeIII ribopatterns were coded for numerical analysis which showed that all except two were different including those of several strains of the same serotype (P2 and P20). At the 30% similarity level, four groupings were formed in the analysis of which three corresponded to C. jejuni, C. coli and C. lari phenotypes respectively. Eight strains (13%) were atypical as their phenotypic and ribopattern associations did not correspond. Ribopattern fragments of 3.0, 5.0 and 9.3 kb were characteristic of the majority of C. jejuni, whereas 1.5, 2.2-, 2.3- and 4.7-kb fragments were commonly present in C. coli. These fragments provided novel species-specific markers. We conclude that HaeIII ribotyping was as discriminatory as Penner serotyping of C. jejuni and C. coli and may even provide a basis for distinguishing between strains of the same serotype and for identifying new groups within the thermophilic campylobacters.

Unintentional carbon monoxide-related deaths in the United States, 1979 through 1988. To describe the epidemiology of recent unintentional carbon monoxide poisoning deaths in the United States. Descriptive analysis of carbon monoxide-related deaths in the United States from 1979 through 1988, based on death certificate reports compiled by the National Center for Health Statistics. All US deaths, 1979 through 1988. We reviewed data from 56,133 death certificates that contained codes implicating carbon monoxide as a contributing cause of death. Of these, 25,889 were suicides, 210 were homicides, 15,523 were associated with severe burns or house fires, and 11,547 were classified as unintentional. The number of unintentional deaths decreased steadily by about 63 deaths per year, from 1513 in 1979 to 878 in 1988. The highest death rates occurred in winter and among males, blacks, the elderly, and residents of northern states. Motor vehicle exhaust gas caused 6552 (57%) of the unintentional deaths; 5432 (83%) of these were associated with stationary automobiles. The rate of unintentional death from carbon monoxide poisoning is decreasing. This may be attributable to improvements in automobile pollution control systems and improved safety of cooking and heating appliances. Prevention programs should target young drivers, males, and the elderly.

Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro. Liposome entrapment of doxorubicin has been shown to reduce its cardiotoxicity in vivo and increase its therapeutic index. A further improvement in therapeutic index could be achieved through targeting of liposome-entrapped drug selectively to cancer cells. Monoclonal antibodies against the squamous lung cancer cell line KLN-205 have been ligated to the surface of long-circulating (Stealth) and conventional liposomes. The antibody-bearing liposomes showed specific, competitive uptake by KLN-205 cells as compared to liposomes bearing nonspecific isotype-matched antibodies or antibody-free liposomes. Doxorubicin-containing antibody-liposomes resulted in as much as a 15-fold decrease in the 50% inhibitory concentration for doxorubicin against KLN-205 cells as compared to free doxorubicin or doxorubicin entrapped in antibody-free liposomes.

Effects of ethanol on pregnant rats and their offspring. Pregnant rats were intubated with either 1.0 or 2.0 g/kg of ethanol daily throughout gestation. Pair-fed vehicle-treated, and nontreated rats fed ad libitum, served as control groups for ethanol-treated animals. Ethanol treatment reduced food and water consumption and attenuated the gain in body weight of pregnant animals relative to nontreated animals fed ad libitum. Litter size, litter weight, and the mean weight per pup were reduced in both the ethanol-treated and pair-fed control groups. There was no evidence of gross malformations in any of the off-spring. Since the reduction in litter size and litter weights did not differ significantly between ethanol-treated and pair-fed controls, the effects of treatment with ethanol appeared to be related to a reduction in maternal intake of calories rather than to the direct effect of ethanol on the developing fetus. There were no significant differences between any of the groups of offspring on one-way shock avoidance learning, water maze escape learning, spontaneous alternation, or brightness discrimination learning in tests beginning at 75 days of age. Thus, at the doses of alcohol used in this study, there was no evidence of behavioral teratogenesis comparable to that reported for higher doses in animals or in man characterized by the fetal alcohol syndrome.

[Applanation tonometry within medical diagnostic "check-up" programs (author's transl)]. Within medical diagnostic "check-up" programs intraocular pressure measurements by applanation tonometry from 8899 patients (5924 men, 66.6%; 2975 women, 33.4%) were statistically evaluated. The frequency of each i.o. pressure show no Gaussian distribution but is skewed to the right with marked excess to higher values of i.o. pressure. Correlation of mean i.o. pressure with age shows (starting in the group of the 20-24 years old to the 75-79 years old persons) a rather linear progression of i.o. pressure. The mean value of i.o. pressure (n = 17,798 eyes) was x = 16.25 mm Hg, the standard deviation +/- 3.45, the standard deviation of the mean +/- 0.03 mm Hg. In men in 2.18% in women in 1.81% higher i.o. pressure than 21 mm Hg was found. I.o. pressure higher than 24 mm Hg have 0.66% of the men and 0.58% of the women. Patients forty years old and elder showing in 4.92% of the men and 4.88% of the women higher i.o. pressure than 21 mm Hg. In patients fifty-five years old and elder in 5.75% of the men and respectively in 6.69% of the women i.o. pressure higher than 21 mm Hg was found. Incidences of elevated i.o. pressure from patients over forty years old in ten years steps are presented. In 103 patients with unilaterally i.o. pressure higher than 24 mm Hg 12% presents manifest diabetes mellitus. The usefullness of applanation tonometry as a practicable screening method for early glaucoma detection within medical diagnostic "check-up" programs is outlined. Advantages of data-aquisition and -processing systems to continue those studies are emphasized.

Structural, molecular, and genetic analysis of the kilA operon of broad-host-range plasmid RK2. The kil loci (kilA, kilB, kilC, and kilE) of incompatibility group P (IncP), broad-host-range plasmid RK2 were originally detected by their potential lethality to Escherichia coli host cells. Expression of the kil determinants is controlled by different combinations of kor functions (korA, korB, korC, and korE). This system of regulated genes, known as the kil-kor regulon, includes trfA, which encodes the RK2 replication initiator. The functions of the kil loci are unknown, but their coregulation with an essential replication function suggests that they have a role in the maintenance or host range of RK2. In this study, we have determined the nucleotide sequence of a 3-kb segment of RK2 that encodes the entire kilA locus. The region encodes three genes, designated klaA, klaB, and klaC. The phage T7 RNA polymerase-dependent expression system was use to identify three polypeptide products. The estimated masses of klaA and klaB products were in reasonable agreement with the calculated molecular masses of 28,407 and 42,156 Da, respectively. The klaC product is calculated to be 32,380 Da, but the observed polypeptide exhibited an apparent mass of 28 kDa on sodium dodecyl sulfate-polyacrylamide gels. Mutants of klaC were used to confirm that initiation of translation of the observed product occurs at the first ATG in the klaC open reading frame. Hydrophobicity analysis indicated that the KlaA and KlaB polypeptides are likely to be soluble, whereas the KlaC polypeptide was predicted to have four potential membrane-spanning domains. The only recognizable promoter sequences in the kilA region were those of the kilA promoter located upstream of klaA and the promoter for the korA-korB operon located just downstream of a rho-independent terminatorlike sequence following klaC. The transcriptional start sites for these promoters were determined by primer extension. Using isogenic sets of plasmids with nonpolar mutations, we found that klaA, klaB, and klaC are each able to express a host-lethal (Kil+) phenotype in the absence of kor functions. Inactivation of the kilA promoter causes loss of the lethal phenotype, demonstrating that all three genes are expressed from the kilA promoter as a multicistronic operon. We investigated two other phenotypes that have been mapped to the kilA region of RK2 or the closely related IncP plasmids RP1 and RP4: inhibition of conjugal transfer of IncW plasmids (fwB) and resistance to potassium tellurite. The cloned kilA operon was found to express both phenotypes, even in the presence of korA and korB, whose functions are known to regulate the kilA promoter. In addition, mutant and complementation analyses showed that the kilA promoter and the products of all three kla genes are necessary for expression of both phenotypes. Therefore, host lethality, fertility inhibition, and tellurite resistance are all properties of the kilA operon. We discuss the possible role of the kilA operon for RK2.

Comparison of kinin-forming and amidolytic activities of four trimucases, oedema-producing and kinin-releasing enzymes, from Trimeresurus mucrosquamatus venom. Four kinin-releasing enzymes, trimucase I, II, III and IV, isolated from Trimeresurus mucrosquamatus venom (TMV) caused rat hind-paw swelling. Trimucase I and III were less potent than trimucase II and IV in this effect. Pretreatment with diphenhydramine or methysergide significantly reduced trimucase-induced paw swelling, while aspirin had no effect. Cellulose sulphate pretreatment suppressed the oedematous responses elicited by trimucases. The residual response was further depressed by diphenhydramine and methysergide. Trimucases also caused kinin generation in-vitro from rat plasma. This kinin-forming activity was in the order of trimucase II greater than IV greater than or equal to III greater than I greater than TMV. All trimucases hydrolysed chromogenic peptides N-benzoyl-Pro-Phe-Arg p-nitroanilide, N-benzoyl-Phe-Val-Arg p-nitroanilide and DL-Val-Leu-Arg p-nitroanilide; the order of this amidolytic activity was trimucase I greater than II greater than III greater than or equal to IV. These data indicate that the effects of venom kinin-releasing enzymes on plasma kininogen are not parallel to their amidolytic effects.

Cardiac rehabilitation services: what are they and are they worth it? The objectives of cardiac rehabilitation include lowering mortality but, more importantly, increasing functional capacity so reducing disability and potentially improving quality of life. The data suggest that cardiac rehabilitation services are worth the patient's costs and efforts and as such, they should be considered an integral component of comprehensive cardiovascular care by cardiologists and primary care physicians. While there is considerable agreement on the roles of exercise testing and training in the three position stands, there are also substantiated, and important, differences in their recommendations on other cardiac rehabilitation services, such as counseling and risk factor management. The challenge for the 1990's is not only to continue to better define the effectiveness of cardiac rehabilitation services, but more urgently, how to deliver effective services most efficiently. This will help physicians provide optimum care for their patients, will improve the patient's likelihood of regaining for themselves an active and productive life, and should generate a more equitable and accountable reimbursement system for quality health care.

Picotamide: effects on coagulation, fibrinolysis and platelet aggregation during prolonged administration in the aged. Picotamide was administered in a daily dose of 1500 mg per os for 30 days to 30 aged, arteriosclerotic subjects and as single doses of 500 mg and 1000 mg to another group of 16 subjects. A reduction of platelet aggregation (methods of Born and Breddin) was observed within 24 hours of commencement of treatment and became more evident in the subsequent days. The reduction was both consistent and significant. A marked increase in fibrinolytic activity (fibrin plate method) was observed during the first 24 hours, particularly for euglobulins with activator. The reaction and clot formation times (r and k) were prolonged and the maximal amplitude (ma) in thrombelastogram was reduced by a definite, though small amount. After the administration of a single dose the maximal effect was observed after eight hours and was still evident after 48 and, to a lesser degree, after 72 hours. The drug was in all cases well tolerated, without any significant side-effects nor untoward reactions.

Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects. Spina bifida and anencephaly are common and serious birth defects. Available evidence indicates that 0.4 mg (400 micrograms) per day of folic acid, one of the B vitamins, will reduce the number of cases of neural tube defects (NTDs). In order to reduce the frequency of NTDs and their resulting disability, the United States Public Health Service recommends that: All women of childbearing age in the United States who are capable of becoming pregnant should consume 0.4 mg of folic acid per day for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other NTDs. Because the effects of higher intakes are not well known but include complicating the diagnosis of vitamin B12 deficiency, care should be taken to keep total folate consumption at less than 1 mg per day, except under the supervision of a physician. Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice.

HCMV-DNA is detected more frequently than infectious virus in blood leucocytes of immunocompromised patients: a direct comparison of culture-immunofluorescence and PCR for detection of HCMV in clinical specimens. In two studies comparing detection of human cytomegalovirus (HCMV) in 118 patients (93 of whom were immunocompromised) by the polymerase chain reaction (PCR) and virus isolation using either early antigen detection by culture-immunofluorescence or conventional cytopathic effect, DNA-PCR was found to be the most sensitive, followed by culture-immunofluorescence, then by cytopathic effect. Urine was inhibitory to the action of Taq polymerase; this was overcome by concentration of HCMV with PEG 6000 prior to gene amplification. Without PEG treatment, HCMV-DNA in 6 of the 11 specimens positive by culture-immunofluorescence was not detectable by PCR. In healthy seropositive individuals, HCMV-DNA was not detected in leucocytes. However, in immunocompromised patients with AIDS or transplants, and therefore at high risk of HCMV infection or reactivation, blood leucocytes were usually positive for HCMV-DNA (19/20), some for as long as 20 weeks after initial detection and persisting for long after culture-immunofluorescence became negative. Neither HCMV-RNA nor infectious HCMV were detected in the follow-up blood leucocyte specimens from immunocompromised patients who had detectable HCMV-DNA in these cells. These data suggest that persistence of HCMV-DNA in blood leucocytes of immunocompromised patients after reactivation or primary infection may be due to persistence of non-viable virus, residual HCMV genomic DNA, or latent HCMV-DNA.

Cephalosporin C acylase in the autolysis of filamentous fungi. Cephalosporin C acylase activity was studied using fluorescamine determination of free--NH2 groups produced in the deacylation of cephalosporin C by the enzyme. Fourteen fungi from different genera were studied and low extracellular cephalosporin C acylase activity was found in the genera Aspergillus, Fusarium and Penicillium. Forty one fungi of these genera were checked but not all presented acylase activity. The enzyme was generally found to be an extracellular enzyme and during the process of autolysis its activity increased with incubation time and with increasing pH of the medium. In no case was beta-lactamase activity detected. Penicillium rugulosum and Penicillium griseofulvum were identified as good cephalosporin C acylase producers. Deacetyl esterase activity was also detected in these fungi.

Guidelines for safety evaluation of cosmetics ingredients in the EC countries. The Scientific Committee on Cosmetology (SCC) of the Commission of the European Communities was established in 1978 to assist the Commission in the application of the 76/768 Directive, which regulates the production and marketing of cosmetics products. The Committee has been asked to update the general guidelines, defined in 1982, for testing cosmetics ingredients with the aim of ensuring consumers' safety. In the present paper the full document approved by the SCC in October 1990 is reported. This new document is based on the experience of the Committee over the last 10 years, during which more than 400 cosmetics ingredients have been evaluated. The document also highlights the need to proceed to define standard methods to be used to assess dermal absorption and phototoxicity--areas in which international guidelines have not yet been approved. The document also includes some comments made by the author in order to explain better the position of the Committee in relation to certain items.

[Infection-induced change in the pharmacokinetics of cefotaxime. Dose calculation in multiple organ failure and relevance of score systems]. The pharmacokinetics of cefotaxime were investigated in 14 patients suffering from multiple-organ failure requiring pump-assisted, continuous volume-constant hemofiltration (CVHF) for blood purification, whereby the filtration rate was 20 ml/min. Samples of blood and ultrafiltrate were evaluated by high-pressure liquid chromatography. For dose adjustment, three different algorithms of Dettli and Kroh were used. As compared with values obtained for anuric patients during the dialysis-free period, the mean serum half-life was nearly doubled (2.75 vs 4.48 h). This reduced elimination depended mainly on a diminished non-renal elimination ratio ranging from 0.085 to 0.366. The volume of distribution remained unchanged within a wide interindividual range (Vz, 0.35 l/kg, from 0.22 to 0.56 l/kg); the sieving coefficient increased to 0.89 as compared with 0.62 in healthy volunteers. Dose adjustment by algorithms showed varied degrees of over-dosage. The estimate closest to an optimal dose was reached by the application of a new algorithm of Kroh (mean dose deviation +19%; SD, +/- 27%) using an individual non-renal elimination ratio (QIND). QIND correlated significantly with the severity of disease according to the sepsis score of Elebute and Stoner (r = 0.763, P less than 0.005). Thus, it is possible to adjust reliably individual dosage in multiple-organ failure and to reduce the frequency of drug monitoring required.

[Osteoarthritis in the light of current research findings]. Chondrocyte and cartilage matrix can in the course of time lose in quality due to nutritive, toxic and enzymatic influences but also due to excessive mechanical usage so that the hyaline articular cartilage can no longer fulfill its function as a hydro-elastic bumper. This results in progressive mechanical cartilage destruction and sclerosing reconstruction of the subchondral bone. The parts of the matrix that are freed by the mechanical abrasion can function as inflammatory mediators and set an accompanying synovitis going. It is this secondary synovitis that then leads to a painful manifestation of osteoarthritis. In this case, an antiphlogistic therapy is necessary, because during a secondary synovitis cytokines are set free that endanger the yet intact articular cartilage.

[Late complications in patients with intraocular lenses]. Examinations were carried out in 222 patients operated for cataract with simultaneous implantation of an intraocular lens. The period of time since the operation amounted 6 to 24 months. The authors observed only minor postoperative complications such as: distortion of the pupil (in 10.8 p.c. of patients), opacification of the posterior lens capsule (2.2 p.c.), a negligible reaction of the iris at the point of contact with the haptic part of the anterior chamber lens (1.4 p.c.), rotation of the lens correctly positioned in the visual axis (0.9 p.c.), incarceration of the haptic part of the anterior chamber lens in the limbal wound (0.9 p.c.), posterior synechiae (0.9 p.c.), occlusion of the pupil by pigment deposits (0.9 p.c.), leakiness of the limbal wound with filtration bleb (0.5 p.c.) and dispersed small deposits of pigment on the anterior surface of the artificial lens. Another complications in the examined patients, known from the literature, were not observed.

Peripheral arteriovenous anastomosis: an alternative technique in a free flap transfer. Prevention of thrombosis in the inflow and outflow vessels of a free flap is a problem of current interest. The method of creating a peripheral arteriovenous anastomosis within a free flap was validated in an experimental study and substantiated in a clinical case. No thrombotic complications were observed in 16 transfers of saphenous fasciocutaneous flaps in a dog model, as well as in an elderly patient with free radial forearm flap transfer to an irradiated foot. Scanning electron microscopy of the venous anastomosis proximal to the arteriovenous fistula revealed the difference of pathologic changes as early as 4 hr following surgery. It is the conclusion of the authors, that performing a distal arteriovenous fistula in a free flap, is an effective procedure for prevention of early occlusion in a proximally anastomosed artery and vein.

Effects of sodium nitroprusside on left ventricular diastolic pressure-volume relations. The effect of sodium nitroprusside on the relationship between left ventricular pressure and volume during diastole was studied in 11 patients with congestive heart failure. Nitroprusside was infused to lower mean arterial pressure approximately 20-30 mm Hg. High fidelity left ventricular pressures were recorded in all patients simultaneously with left ventricular cineangiography (biplane in eight and single plane in three patients), allowing precise measurement of pressure and volume throughout the cardiac cycle. Left ventricular diastolic pressure-volume curves were constructed in each patient from data obtained before and during nitroprusside infusion. In 9 of 11 patients there was a substantial downward displacement of the diastolic pressure-volume curve during nitroprusside infusion, with left ventricular pressure being lower for any given volume with nitroprusside. Serial left ventricular cineangiograms performed 15 min apart in six additional subjects who did not receive sodium nitroprusside showed no shift in the diastolic pressure-volume relation, indicating that the shift seen with nitroprusside was not due to the angiographic procedure itself. A possible explanation for the altered diastolic pressure-volume relationships with nitroprusside might be a direct relaxant effect of nitroprusside on ventricular muscle, similar to its known relaxant effect on vascular smooth muscle. Alternatively, nitroprusside may affect the diastolic pressure-volume curve by affecting viscous properties or by altering one or more of the extrinsic constraints acting upon the left ventricle.

Uses of data to plan cancer prevention and control programs. Seven State health departments, those in Illinois, Nebraska, New Jersey, New York, North Carolina, Texas, and Wisconsin, have participated in an effort to utilize a variety of State-specific cancer-related data to describe the cancer burden in their State's population. The data were then used to develop a statewide cancer plan or supplement an existing plan to address the defined problems. Cancer data have not been well utilized in the planning of intervention programs in the past, and the efforts in these States can serve as models for data use in programs to prevent and control cancer and other chronic diseases. State-specific data can be used to rank needs and make a clear case that can influence decision makers regarding resource allocation. The purpose of this report is to describe the data sources and additional statistics that were used to provide a broad picture of the cancer burden that will aid in targeting and defining intervention needs. Mortality, incidence, risk factor prevalence, and hospital discharge data appear to be the most accessible and potentially useful of the data sources examined, whereas insurance claims data, sources of treatment data, and environmental data bases were less useful in planning intervention strategies.

Uptake of glucuronides into isolated hepatocytes and their effects on glucuronide and sulphate conjugation. Uptake studies, using radioactive labelled glucuronides, have demonstrated the ability of 4-nitrophenyl glucuronide and phenolphthalein glucuronide to enter isolated rat hepatocytes. Of these glucuronides 4-nitrophenyl glucuronide was distributed in a similar manner to O-methylglucose, whereas phenolphthalein glucuronide was bound to cellular constituents. Phenolphthalein glucuronide had an effect on theconjugation of harmol in the isolated hepatocytes when glucuronidation was found to be markedly inhibited and sulphation slightly stimulated. The glucuronidation of 4-nitrophenol, 4-methylumbelliferone and harmol in native microsomes was inhibited by phenolphthalein glucuronide. 4-Nitrophenyl glucuronide and also naphthyl glucuronide were without effect both in hepatocytes and microsomes. In control hepatocytes harmine was metabolized to form harmolsulphate mainly. Phenolphthalein glucuronide only affected this metabolic pattern to a minor extent. However, in hepatocytes from phenobarbital treated rats, where the rate of harmine metabolism is increased about five times and the main metabolite is harmol glucuronide, phenolphthalein glucuronide inhibited the formation of the conjugate with a concomitant increase in free harmol.

Comparison of erythrocyte membrane Ca2(+)-Mg2(+)-ATPase activity in children with and without family history of essential hypertension. The causes of elevated intra-erythrocyte calcium in the offspring of essential hypertensive patients are unknown. Fourteen children with and without a family history of essential hypertension were chosen to compare erythrocyte membrane Ca2(+)-Mg2(+)-ATPase activity (Rbc-M Ca2(+)-Mg2(+)-ATPase activity) measured by biochemical methods. We found that Rbc-M Ca2(+)-Mg2(+)-ATPase activity was lower in children with family history of hypertension compared with children with no family history (2.16 +/- 1.10 vs 3.36 +/- 1.19 microM Pi/mg protein/hour P less than 0.01). These results suggest that the reduced Rbc-M Ca2(+)-Mg2(+)-ATPase activity may be one of the mechanisms causing the high erythrocyte calcium levels in the offspring of essential hypertensive patients.

Selenium in human mammary carcinogenesis: a case-referent study. In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms/l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels revealed no association between selenium levels and breast cancer risk.

Evaluation of degenerative lesions of the rotator cuff. A comparison of arthrography and ultrasonography. A prospective study was performed to determine the accuracy of arthrography compared with ultrasonography in the evaluation of thirty-two patients who had a degenerative lesion of the rotator cuff. Both tests were done preoperatively, and the condition of the rotator cuff was determined intraoperatively. Arthrography was accurate in the diagnosis of twenty-eight (87 per cent) of the thirty-two patients (twenty who had a full-thickness tear, seven who had a partial-thickness tear, and five who had an untorn rotator cuff and tendinitis), while ultrasonography was diagnostic in only twelve (37 per cent). In this specific population of patients, arthrography was found to be superior to ultrasonography.

Fiberoptic bronchoscopy. Comparison of procedures used in the diagnosis of lung cancer. We have compared the relative value of various techniques used in association with fiberoptic bronchoscopy for the diagnosis of lung cancer. We analyzed the results in 114 patients who underwent diagnostic fiberoptic bronchoscopy and in whom a definite histologic diagnosis of lung cancer was made. A comparison of the diagnostic yield from cytologic examination of prebronchoscopy and postbronchoscopy sputum and of fiberoptic bronchial biopsy, brushing, and washing was made. Over-all, bronchial washings gave the highest diagnostic yield (75.4%) and forceps biopsy the next higher (65.8%). The combination of bronchial washings and forceps biopsy gave the highest diagnostic yield (95.8%). In six patients, postbronchoscopy sputum was the only source of positive diagnostis; in 20 patients only one procedure was positive. Our results suggest that although fiberoptic bronchoscopy washings and forceps biopsy have the highest diagnostic yield, brushings and postbronchoscopic sputum examination are also important diagnostic maneuvers and should be routinely performed.

Alternative forms of Max as enhancers or suppressors of Myc-ras cotransformation. Max is a basic-helix-loop-helix-leucine zipper protein capable of forming sequence-specific DNA binding complexes with Myc proteins. An alternatively spliced messenger RNA has been identified that encodes a form of Max truncated at the COOH-terminus. This delta Max protein retained the ability to bind to the CACGTG motif in a complex with c-Myc but lacks the nuclear localization signal and the putative regulatory domain of Max. When tested in a myc-ras cotransformation assay in rat embryo fibroblasts, Max suppressed, whereas delta Max enhanced, transformation. Thus, the max gene may encode both a negative and a positive regulator of c-Myc function.

Actin and tubulin binding domains of synapsins Ia and Ib. Synapsins Ia and Ib are neuronal phosphoproteins involved with the regulated clustering of small synaptic vesicles at the presynaptic terminus. In vitro they bind and bundle filaments of both actin and tubulin. Previously, we identified an actin binding domain in the NH2-terminal 25-kDa fragment (N25) generated by 2-nitro-5-thiocyanobenzoic acid (NTCB) cleavage of synapsin I and found that a complementary COOH-terminal 52-kDa portion of the molecule (N52) contained either a second actin binding site or a site of self-association [Petrucci, T. P., & Morrow, J. S. (1987) J. Cell. Biol. 105, 1355]. Using direct binding assays between actin, tubulin, and specific synapsin NTCB-derived peptides, we confirm the ability of purified N25 to bind but not bundle actin and demonstrate that the complementary N52 (or N50) fragments from synapsins Ia and Ib and a 14-kDa fragment derived from the middle of the molecule also associate directly with actin. An antibody specific for N25 inhibits the actin binding activity of N25 and the actin bundling but not the actin binding activity of intact synapsin I. Similar studies conducted with purified tubulin and tubulin immobilized on Sepharose demonstrate that both tubulin and actin bind at approximately the same sites in the NH2-terminal half of synapsin I. Although the fragments derived from the COOH terminus of both synapsin Ia and synapsin Ib (N40b/N34) were devoid of measurable actin binding activity after NTCB cleavage, they were specifically labeled in the intact molecule by a photoactivated cross-linker bound to F-actin. Collectively, these results indicate that synapsins Ia and Ib possess two actin and tubulin binding domains located in the NH2-terminal half of the molecule and suggest that a third actin binding domain is located in the COOH-terminal region. The NH2-terminal sites are found in NTCB peptides N25 and N14, while the third site, apparently of lower affinity, resides in N40b/N34. It is hypothesized that, in the intact molecule, the two NH2-terminal domains contribute to a single high-affinity actin and/or tubulin binding site in the "globular" head region of synapsin I, while the third actin binding domain constitutes the topographically distinct site required for the actin bundling activity of the native molecule. The 45-residue COOH extension that distinguishes synapsin Ia from synapsin Ib appears not to be involved with actin binding, since no differences were found in the ability of N40b and N34 to be photo-cross-linked to actin.(ABSTRACT TRUNCATED AT 400 WORDS)

Nucleoside phosphotransferase of chick embryo. This paper describes a purification procedure and some properties of a nonspecific nucleoside phosphotransferase of chick embryo, an activity which catalyzes the transfer of chick embryo, an activity which catalyzes the transfer of the phosphate ester from a deoxyribonucleotide or a pyrimidine ribonucleotide to a deoxyribonucleoside acceptor. The enzyme is very unstable to heat, dilution and dialysis and it is almost entirely inactivated by DEAE-cellulose chromatography or gel filtration. A marked enhancement in its stability is caused by numerous nucleotides. In these experiments at least 920-fold purification was obtained by using dTTP (50 microM) as nucleotide protector. The enzyme, purified in presence of dTTP, has a molecular weight about 270,000, an isoelectric point of 6.27, a pH optimum of 8.8 and is stable at 37 degrees C at least for 10 min. In absence of nucleotide protector, nucleoside phosphofranserferase is connected at 37 degrees C or by gel filtration in a very small active form with a lower molecular weight (about 30,000) and a pH optimum of 7.6.

Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site. A synthetic decapeptide, P-194, which has the sequence No. 103 to 111 of hTSH receptor structure with an additional N-terminal tyrosine, did not bind TSH nor affected its receptor binding and thyroid stimulating activity. Preincubation of P-194 with sera from thyroid patients caused a significant decrease in TBII activity in almost all 12 TBII positive sera and an increase of thyroid stimulating activity in 3 of 7 Graves' IgG studied. In addition, [125I] P-194 bound to serum IgG fraction from thyroid patients with a positive correlation with TBII (N = 35, r = 0.509, p less than 0.01). The P-194 portion may be, at least a part of, TBII binding site distinct from the TSH binding site on the TSH receptor.

Human T-lymphotropic virus type I infection in the Solomon Islands. To ascertain the prevalence of human T-lymphotropic virus type I (HTLV-I) infection and the occurrence of diseases caused by HTLV-I in the Solomon Islands, we tested 1141 sera from 851 patients (317 females and 534 males), who were hospitalized at the Central Hospital in Honiara between February 1984 and November 1988, for antibodies to HTLV-I using an enzyme-linked immunosorbent assay (ELISA). Sera from 69 of 81 ELISA-positive patients and from 56 ELISA-negative patients were then tested by Western analysis. As verified by strict Western immunoblot criteria, the overall HTLV-I seroprevalence was 2.2% (19/851). Age- and gender-specific prevalence data indicated an age-related acquisition of infection with no sexual predominance. No diagnosis category was over-represented among the seropositive patients. HTLV-I-specific antibodies were found in serum and cerebrospinal fluid samples from one of six patients with spastic paraparesis. As in other Melanesian populations, the majority of ELISA-positive sera could not be confirmed by Western analysis. Reactivity to three or more gag-encoded proteins was found in 85% (45/53) of ELISA-positive, Western blot-indeterminate sera, and 30% (16/53) reacted to p19 and an env gene product but lacked reactivity to p24. Whether or not the high frequency of indeterminate HTLV-I Western immunoblots in the Solomon Islands is indicative of incomplete specific reactivity to HTLV-I or the existence of antigenically related retroviruses is being investigated.

Serial casting as a technique to correct burn scar contractures. A case report. Serial casting is a fast, relatively simple, and inexpensive way to effectively correct burn scar contractures. Plaster casts provide circumferential pressure and a prolonged stretch to contracted tissue and cannot be removed by the patient. When casts are applied well and padded appropriately, there is little risk of pressure areas, since the casts are conforming and do not slip distally. Serial casting may be a successful alternative when low-force dynamic splinting cannot be sized small enough for a child, or when patient compliance is unreliable. A case study of a 2-year-old male patient with severe plantar-flexion contractures of the ankles is presented.

Serum estradiol response to gonadotropin-releasing hormone: studies in normal women and in women with secondary amenorrhea. Serum estradiol (E2), luteinizing hormone (LH), and follicle stimulating hormone (FSH) levels were measured in blood samples obtained prior to and at frequent intervals for 360 or 480 minutes following the subcutaneous administration of gonadotropin releasing hormone (Gn-RH) to eight normal women and nine patients with hypothalamic secondary amenorrhea. In the normal subjects given 100 mug of Gn-RH on day 7 of the menstrual cycle, there was no significant increase in the mean E2 concentration above basal levels. Six women with secondary amenorrhea received Gn-RH, 100 mug, for 4 successive days; frequent blood samples were obtained on days 1 and 4. On day 1, the mean E2 concentration at 360 minutes was significantly greater than the mean basal level. On day 4 no significant increase in E2 was detected, although the mean LH and FSH responses and basal E2 level were not different from those of day 1. Four women with secondary amenorrhea received daily doses of 500 mug of Gn-RH for 7 days. Significant increases in mean serum E2 concentration (100 to 150 pg/ml) were noted at 6 and 8 hours after administration on day 1 and at 8 hours on day 4. No significant rise in E2 was detected on day 7. The mean LH and FSH responses did not differ from those observed in women who received the 100-mug dose, and there were no significant differences in responses on successive days of Gn-RH administration.

Protein kinase of bacteriophage T7 induces the phosphorylation of only a small number of proteins in the infected cell. Bacteriophage T7 expresses a serine/threonine-specific, cAMP-independent protein kinase activity encoded by the early gene 0.7. The phosphoproteins specifically resulting from gp0.7 protein kinase expression in T7-infected Escherichia coli have been examined by one-dimensional, SDS-polyacrylamide gel electrophoresis. Only seven major, stable phosphoproteins dependent on gp0.7 protein kinase expression are observed. Two of the gp0.7 protein kinase-specific phosphoproteins observed have been previously identified: the beta' subunit of RNA polymerase and the RNA processing enzyme RNase III. The gp0.7-catalyzed protein phosphorylation activity appears at 9-11 min postinfection at 30 degrees. The new phosphoproteins have a metabolic stability comparable to that of uninfected cell phosphoproteins. T7 protein kinase expression causes the phosphorylation of the same, limited set of proteins in B, C, or K strains of E. coli. Expression of the T3 and BA14 phage protein kinase activities also produces the same phosphoproteins.

Autoradiographic localization of 125I-galanin binding sites in the blowfly brain. The localization of porcine galanin (pGAL) binding sites in the brain of the blowfly Phormia terraenovae was investigated by autoradiography using the following radioiodinated ligands: pGAL 1-29 (two isoforms), pGAL 15-29 and rat (r) GAL 1-29. The different porcine radioligands bound specifically with the following intensity: 125I-[Tyr26]-pGAL15-29 > > 125I-[Tyr26]-pGAL1-29 > > 125I-[Tyr9]-pGAL1-29. With rat galanin 125I-[Tyr9]-rGAL1-29 no specific binding could be shown. In addition, displacement of 125I-[Tyr26]-pGAL1-29 was tested with pGAL 1-29, pGAL 1-22 and pGAL 15-29 (at 0.1 nM-1 microM). A gradual displacement was achieved with increasing concentrations of pGAL 1-29 and pGAL15-29, whereas no displacement with pGAL 1-22 was detected. The results indicate that the C-terminal portion of pGAL is important for binding in the blowfly. The pGAL binding sites were localized in synaptic neuropils of the central body, the antennal lobes, the optic lobes, the pars intercerebralis and the subesophageal ganglion, all of which contain GAL-like immunoreactive neural processes.

Punch shear strength of polycarboxylate cements. Two general conclusions are drawn which apply to all the four commercial polycarboxylate cements: First, the effect of storage condition upon shear strength was much more pronounced after 24 hours than after 1 hour of storage time; second, the effect of storage condition was most extreme when the specimens were tested free of their matrices. Additionally some specific comparisons between the four products tested can be made based on differences of shear strength within the same experimental condition. The effect of confinement decreased in the following order: Boston greater than Bondal greater than PCA greater than Durelon. Sensitivity to storage conditions decreased in this order: Durelon greater than Bondal greater than PCA greater than Boston. Finally sensitivity to storage times decreased in the order Bondal greater than Durelon greater than Boston greater than PCA.

Aeromedical transportation for infants and children. Transfer of a critically ill child to a pediatric center is indicated when patient needs have exceeded local expertise or facilities. It is illogical to impose on the referring hospital the added burden of transporting such a patient. The receiving hospital is better equipped to extend its specialized services by assuming responsibility for interim management and transfer of the patient. An aeromedical transport system capable of quick response was built around National Guard helicopters. In 21 cases, doctors, nurses, and equipment were flown to children in community hospitals, and urgent treatment was begun in half the time formerly possible. Only after the patients were stabilized were they returned safely under continuing appropriate management. The helicopter is a versatile and speedy tool to deliver expertise and equipment when and where needed. Timely arrival of specialty services can be expected to improve patient care and salvage.

Demonstration of anti-"a-component" antibody--a possible means to differentiate patients with auto-antibodies to endogenous insulin from insulin-treated patients. The presence of anti-"a-component" antibody was examined in sera of 4 groups of patients with or without anti-insulin antibody, using 125I-a-component and the polyethylene glycol precipitation method. 125I-a-component crossreacted with insulin antibody. This cross-reactivity was abolished after preincubation of these sera with monocomponent insulin. The specificanti-"a-component" antibody could be estimated in this procedure. After preincubation with monocomponent insulin, significant binding of 125I-a-component was demonstrated in sera of most patients treated with ordinary commercial insulin, but not in sera of 2 hypoglycemic patients suspected of an insulin autoimmune syndrome. Some cases treated with commercial insulin for less than one year and all cases treated with monocomponent insulin for 7-10 months did not have significant anti-"a-component" antibody. The test for the presence of anti-"a-component" antibody is not definitive but if positive it differentiates "auto-antibodies" from the antibodies produced by injections of commercial insulin.

Variable expression of vision in sibs with albinism. Oculocutaneous albinism is defined by the presence of cutaneous and ocular hypopigmentation, the latter associated with nystagmus, iris transillumination, reduced retinal pigment, foveal hypoplasia, and misrouting of the optic fibers at the chiasm. The visual acuity is variable but almost always reduced. We report on two brothers with oculocutaneous albinism and markedly different visual acuity. One brother has a visual acuity of 20/100, while the second has similar cutaneous pigmentation and visual acuity of 20/20 and had not previously been recognized as having oculocutaneous albinism. Both brothers have foveal hypoplasia and misrouting of the optic fibers at the chiasm. Biochemical analysis suggests that this is a tyrosinase-related type of oculocutaneous albinism. This study demonstrates that careful observation of foveal development in relatives with normal vision is necessary to detect all individuals with albinism in a family. A suspected diagnosis of albinism may be confirmed when the visual-evoked potentials show excessive decussation of the optic fibers at the chiasm.

Potassium toxicity and acid-base balance from large oral doses of potassium to young calves. Potassium chloride and sodium chloride were infused into the reticulorumen of male Holstein calves, approximately 6 mo of age and 260 kg, at .29, .58, 1.15, 1.73, 2.31, or 2.88 g potassium per kilogram body weight or 1.35, 2.12, or 2.16 g sodium per kilogram in equal volumes of water. Paired controls were infused with water. Calves were monitored for physiological changes for 6 h at 15, 30, or 60-min intervals. Potassium and total solids of plasma and packed cell volume were increased at potassium doses greater than .29 g of potassium per kilogram body weight within 1 h after dosing. At the higher doses of potassium, sodium content of plasma increased about 1 h after the increase in plasma potassium. Respiration rates within a potassium treatment varied with respect to time after dosing, but generally they increased, and associated variables of carbon dioxide pressure, pH, and bicarbonate in blood were decreased accordingly. Clinical toxicity signs, including excess salivation, muscular tremors of legs, and excitability were observed with potassium doses greater than .58 g of potassium per kilogram body weight. Three of five calves given 1.73 g of potassium per kilogram, three of four calves given 2.31 g of potassium per kilogram, and one calf given 2.88 g of potassium per kilogram body weight died. With a small number of calves, oral sodium infusions increased plasma sodium in proportion to the dose, but plasma potassium remained relatively constant. Sodium infusions of 2.12 and 2.16 g of sodium per kilogram body weight were fatal.

Atrial natriuretic peptide and vasopressin during percutaneous transvenous mitral valvuloplasty and relation to renin-angiotensin-aldosterone system and renal function. To study the relation between plasma atrial natriuretic peptide (ANP) and cardiac pressure, and to assess the pathophysiologic significance of ANP in water and electrolyte metabolism, the changes in plasma levels of ANP and arginine vasopressin (AVP) were examined in 11 patients with mitral stenosis who underwent percutaneous transvenous mitral valvuloplasty, and compared with the changes in the renin-angiotensin-aldosterone system and renal function. Immediately after valvuloplasty, plasma ANP levels decreased significantly with a concomitant decrease in mean pressures in the left atrium, the pulmonary artery and the right atrium. Plasma ANP levels decreased to the normal range in 4 of the 6 patients with normal sinus rhythm, while all 5 patients with atrial fibrillation had higher levels despite a similar degree of decrease in atrial pressure. There were significant positive correlations between plasma ANP levels and the mean left atrial pressure (r = 0.61, p less than 0.01), the mean pulmonary arterial pressure (r = 0.49, p less than 0.01) and the mean right atrial pressure (r = 0.54, p less than 0.01). The mean plasma AVP levels, on the other hand, showed a transient increase after valvuloplasty from 0.5 +/- 0.1 to 1.2 +/- 0.4 pg/ml (p less than 0.05). The mean plasma renin activity (1.3 +/- 0.3 vs 2.7 +/- 0.8 ng/ml/hr, p less than 0.05) and plasma aldosterone concentration (8.6 +/- 2.3 vs 17.2 +/- 5.2 ng/dl, p less than 0.05) also increased significantly 30 minutes after valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Human mammary tumor cell proliferation: primary role of platelet-derived growth factor and possible synergism with human alpha-fetoprotein. Human mammary medullary carcinoma cells (passages 16 to 21) were cultured for 2 days to allow for attachment, followed by 6 days of culture in either fetal calf serum, human cord blood, human amniotic fluid, or growth factors in the presence or absence of purified human alpha-fetoprotein (AFP). When growth factors were tested alone, only platelet-derived growth factor produced a significant increase in cell proliferation. Although up to 40% amniotic fluid had no effect on cell proliferation, human cord blood was two-fold more potent than fetal calf serum at similar concentrations. The addition of 10 ng/ml of platelet-derived growth factor increased the proliferative activity of human cord blood 1.5- to 2.5-fold. Ablation of endogenous AFP by affinity chromatography reduced the proliferative activity of cord blood by 75%. Similarly, the mitogenic activity of cord blood plus platelet-derived growth factor was reduced by 56% when AFP was removed. Purified AFP dose-dependently enhanced the proliferative activity of platelet-derived growth factor. This synergistic effect was specific for platelet-derived growth factor. We conclude that platelet-derived growth factor is a major growth factor controlling the proliferation of these tumor cells and that AFP may enhance growth factor proliferative activity and human mammary tumor growth.

Measurement of inactive renin in normal, nephrectomized, and adrenalectomized rats. In a new method for measurement of inactive rat plasma renin, the trypsin generated angiotensin I immunoreactive material, which was HPLC characterized as similar to tetradecapeptide renin substrate, is removed by a cation exchange resin before the renin incubation step. The method also corrects for trypsin destruction of endogenous angiotensinogen by the addition of exogenous angiotensinogen. When measured with this method inactive renin in rat plasma decreased after nephrectomy and increased after adrenalectomy. This is in accordance with findings in humans. A sexual dimorphism of prorenin (inactive renin) in rat plasma, similar to that reported in humans and mice, was demonstrated. Thus, inactive renin in the rat is no exception among species, and the rat might be a suitable animal model for further studies dealing with the physiology of prorenin in plasma and tissues.

Comparative study of the effect of CV-6209, a specific PAF-antagonist, on rat paw edema caused by different phlogogen agents. Comparative effects of CV-6209, a potent and specific platelet activating factor (PAF) antagonist, on PAF-acether-, carrageenin-, histamine-, serotonin-, compound 48/80-, dextran-, zymosan A- and arachidonic acid-induced rat paw edema were investigated. CV-6209 has proven to be effective in PAF-induced edema, but it also showed a significant activity in other models of paw edema, except those induced by zymosan A and arachidonic acid. Other drugs tested, namely indometacin, mepyramine, methysergide and nordihydroguaiaretic acid showed a more selective inhibitory profile. These results suggest an important role of PAF in the inflammatory process caused by intraplantar injection of different phlogogenes in the rat paw.

The clearance rate of exercise-elevated blood lactate following physical training. In this paper, previous studies regarding the effect of physical training on the disappearance rate of blood La during recovery after strenuous exercise have been briefly summarized. The results of our own recent study of this problem have also been added. It may be concluded that there is some evidence for an improved lactate metabolic clearance rate resulting from physical training in human subjects, when the degradation rate is estimated from serial blood samples taken during a standard ramp ergometer test to exhaustion during each week of a training/detraining sequence. This beneficial effect of training, however, may also be influenced by the initial physical status of the subject and the nature of the training program.

Continuous spectrophotometric measurements of arteriovenous oxygen difference. A relatively inexpensive dual-beam optical absorbance monitor was tested and adapted to measure arterio-enous oxygen difference ((a - v)delta O2). Since the molar extinction coefficients of oxy- and deoxyhemoglobin are markedly different at 660 nm, the difference in optical density between arterial and venous blood, as measured by the absorbance monitor, was shown to be linearly related to (a - v)delta02. When appropriate cuvettes (optical path length = 0.5 mm) were used, the instrument's 90% response time (4.4 s) was sufficiently rapid for most physiological applications such as Fick determinations of the rate of an organ's oxygen consumption. The theoretical basis of this spectrophotometric (a - v)deltaO2 measurement and sources of error are discussed in detail.

[Diaplacentar transfer of local anaesthetics (author's transl)]. A very rapid resorption of the amide-type local anaesthetic agents most commonly used in obstetrics results in detectable plasma levels in mother and fetus within 5 to 10 minutes, respectively, after peridural anaesthesia. The various local anaesthetics differ from each other as far as their protein-binding capacity and the resulting ratios of umbilical vein to maternal blood levels are concerned. The feto-maternal ratio is inversely correlated to the degree of protein-binding. Both, the protein-binding capacity and the feto-maternal ratio do not indicate the total amount of the anaesthetic transferred across the placenta. In contrast to measurements of the plasma concentrations only the measurement of the anaesthetic in the fetal tissue would give an exact information about the fetal uptake of local anaesthetics. Several observations hint at the possibility that there are interactions between local anaesthetics and other drugs: A competitive displacement of local anaesthetics from their protein binding sites resulting in an increase in the unbound fraction is suggested. Since the feto-maternal equilibration exists only for the unbound fraction interactions of local anaesthetics with simultaneously administered drugs should be taken into consideration.

Urinary excretion of NAG and FDP in acute renal graft rejection. Determination of the urinary excretion of N-acetyl-D-glucosaminidase (NAG) and fibrin degradation products (FDP) made it possible to make a diagnosis of 25 out of 26 acute rejection episodes at least 24 hr before deterioration in renal function occurred. Of the two tests, the estimation of daily urinary NAG is the most practical for routine clinical use. This test alone permitted early diagnosis in 21 out of 26 episodes. In 9 out of 11 episodes in which both estimations showed an increase, the rise in FDP occurred before the rise in NAG. This is consistent with the view that in some forms of rejection, at least, intravascular fibrin deposition occurs first and causes ischaemic damage to renal tubular cells and consequent deterioration in function.

Measurement issues in evaluating physicians' practice patterns using hospital billing and surgeon's self-report data. The availability of computerized case mix data, which merge medical records information and patient billing data, provide opportunity for measuring physician-specific practice patterns. However, the validity of physician comparisons is a concern when total patient charges are measured at two points in time. In this physician-initiated multicenter study, comparisons using samples of uncomplicated, baseline cases, as determined from medical records chart reviews of five surgical procedures at three institutions, demonstrated a statistically significant reduction in average length of stay (ALOS) from 0.8 to 2.8 in seven of the 15 studies while total patient charges increased in 11 of the studies from one to 29 per cent. Billing data were useful in measuring ALOS and the frequency of specific laboratory tests ordered and then comparing these to physicians' self-report practice.

Accumulation of [3H]-inositol into inositol polyphosphates during development of Dictyostelium. Inositol hexakisphosphate (InsP6) is present in large amounts during the development of Dictyostelium discoideum although its function is unknown. We have investigated the accumulation of [3H]-labelled inositol into both InsP6 and a more highly charged inositol species called InsPY during development of amoebae on filters. We report that the pattern of [3H]-labelled inositol incorporation into InsP6 and InsPY differs markedly from the pattern seen for inositol phospholipids and inositol(1,4,5)trisphosphate. Incorporation into PtdIns, PtdInsP, PtdInsP2 and Ins(1,4,5)P3 reached plateau values within 4 h. In contrast, incorporation into InsP6 continued in an approximately linear manner for the first eight hours of development. No incorporation into InsPY was seen during the first three hours of development at which time accumulation of [3H] continued linearly in a similar manner as for InsP6. Because the total cell concentration of InsP6 (measured by chemical assay) changes very little during development it seems probable that incorporation of label into InsPY after 3 h is due to a developmentally controlled metabolic switch rather than a requirement for a threshold level of its probable precursor, InsP6.

Molecular characterization of an Enterobacter cloacae gene (romA) which pleiotropically inhibits the expression of Escherichia coli outer membrane proteins. The introduction of a newly cloned Enterobacter cloacae chromosomal gene romA, into Escherichia coli and E. cloacae resulted in enhancement of resistance to quinolones, beta-lactams, chloramphenicol, and tetracycline. The primary effect of romA on a multicopy vector in E. coli was almost complete inhibition of OmpF expression in the outer membrane. From the experiments with ompR and envZ mutants or with ompF-lacZ and ompC-lacZ fusion plasmids, it was concluded that this inhibition is posttranscriptional. The introduction of romA on a multicopy vector into strains with micF deletion elicited only a moderate decrease in OmpF protein expression. This indicates that reduction of OmpF expression by romA is partly mediated posttranscriptionally by the activation of micF. Moreover, the overexpression of RomA protein from an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoter resulted in nearly complete inhibition of expression of OmpC and OmpA, as well as OmpF. Taken together with an observation in a recent study that overexpressed OmpC inhibited the synthesis of OmpA and LamB, a possible inhibitory mechanism at the translational stage of the synthesis of outer membrane proteins should also be considered. By Southern hybridization, romA was generally detected in the chromosomes of all E. cloacae strains tested but not in the E. coli K-12 chromosome. Sequence data show that there is an open reading frame specifying 368 amino acids residues including a putative signal peptide. RomA appears to belong to the outer membrane protein family since it was extractable from an outer membrane preparation, but no sequence homology to other outer membrane proteins was detected.

Early and late lesion-to-non-lesion ratio of thallium-201-chloride uptake in the evaluation of "cold" thyroid nodules. Forty-nine consecutive patients with "cold" thyroid nodules were studied using early and late visual and semiquantitative measurements of 201Tl uptake in the nodule to differentiate benign from malignant nodules. The visual method compared 201Tl uptake in the nodule to the normal thyroid tissue. The semiquantitative method used a lesion-to-non-lesion (L/N) ratio of the same areas. Both measurements were carried out early (15 min) and late (3 hr) following 201Tl injection. The reproducibility of the method for the early and late measurements was tested for intraobserver and interobserver variability as well as for repeatability coefficients. The visual method resulted in 43% sensitivity and 79% specificity for the detection of malignant nodules. The L/N method showed that an early threshold of 1.55 chosen by receiver characteristic analysis had a sensitivity of 57% and a specificity of 86%, while the late ratio of 0.99 had a sensitivity of 100% and a specificity of 62%. It is concluded that a L/N 201Tl uptake method performed 3 hr following 201Tl injection is superior to a visual scoring method as well as to the early L/N 201Tl uptake in detecting malignant thyroid nodules.

Differential passage rates and digestion of neutral detergent fiber from grain and forages in 30, 60 and 90% concentrate diets fed to steers. Six ruminally cannulated steers were used to determine the effects of altering dietary concentrates on fiber digestion. Diets contained 30, 60 or 90% of a concentrate based on flaked sorghum grain plus a 50:50 mixture of wheat straw and alfalfa hay. Total tract digestibility of NDF was not altered, but digestibility of potentially digested NDF (PDF) decreased (P less than .05) from 92 to 48% as concentrates increased from 30 to 90% of diet DM. Ruminal passage rate for straw (3.4 and 3.0%/h) and for hay (4.6 and 4.7%/h) was unchanged when concentrate was increased from 30 to 60%, but it decreased by 28 (2.2%/h) and 13% (4.1%/h), respectively (P less than .05), when concentrates were increased to 90%. Passage rate for grain (5.3, 5.1 and 4.4%/h) and fluid (9.3, 10.0 and 8.2%/h) was not influenced by concentrate percentage. Calculated ruminal digestibilities of NDF in individual ingredients did not differ between 30 and 60% concentrates, but they decreased (P less than .05) by 72, 57 and 34% for straw, hay and grain when concentrate was increased to 90%. Because of their relative contribution to total diet NDF, straw, hay and grain accounted for 28, 18 and 54% of the total decrease in estimated fiber digestion. It is concluded that PDF as well as NDF should be evaluated in studies of concentrate effects on fiber digestion, and that dietary concentrate level has more influence on passage rate of low-quality forage than on passage rate of grain or high-quality forage. In 90% concentrate diets, although fiber digestibility was depressed more for forage than for grain, grain accounted for most of the depression in fiber digestion because grain was the primary source of dietary fiber.

The selection of laboratory equipment. The last few years have seen dramatic changes in laboratory haematology. Technological developments with increasing levels of automation have resulted in a plethora of new instruments. The choice of which to buy, often confused by conflicting advice and persuasive salesmanship, must be balanced by the need for cost containment. This calls for an understanding of the principles of selection to ensure that the system that is chosen will provide reliable results in the most efficient manner at the lowest possible cost. Most of the instruments which are currently available perform their intended tasks reasonably well albeit with some inter-instrument differences, usually due to different operating procedures and different methods of calibration. The task is to find a system that performs the required tests correctly and reliably, fits into the work requirements of the laboratory and is accepted by the staff who will operate it, whilst its cost both capital and recurrent, should be within the department's financial constraints. The selection of laboratory equipment is thus a complex and time consuming task.

Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma. Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewing's sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients.

Sialogluciduria in lysosomal diseases: quantitative and qualitative analysis of urinary low molecular sialoglucides from patients with mucopolysaccharidosis and with mucolipidosis. Low molecular sialoglucides were isolated from the urines of normal human male and two patients with lysosomal disease (mucopolysaccharidosis type II and a new type of mucolipidosis) by charcoal adsorption method. Urinary sialoglucides were fractionated into two fractions (SG-1 and SG-2) by Sephadex G-25 gel filtration and considerable increase in excretion of SG-1 was observed in the patients with lysosomal diseases: two- to three-fold increase in mucopolysaccharidosis type II and seven- to eight-fold increase in mucolipidosis. SG-1 was further fractionated into 18 to 19 fractions by Sephadex G-50 gel filtration and ion exchange chromatography. Comparison of the amounts and the chemical compositions of these fractions suggested that the increase in SG-1 was dependent upon the increase in excretion of low molecular sialoglucides rich in mannose and N-acetylglucosamine.

Thromboembolic risk in children with nephrotic syndrome. The in vivo activation of the hemostatic system was evaluated in 14 children (4-13 years old) with nephrotic syndrome at different stages of the disease. The blood platelet count, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), fibrinogen, the coagulation inhibitors antithrombin III and protein C (ATIII:Ag and PC:Ag), and D-dimers were determined. Platelet number was significantly higher at the onset of the disease than in the next stages (p less than 0.05). beta-TG, PF4 and fibrinogen were significantly increased as compared with controls at the onset (p less than 0.001) and decreased progressively during the course of the disease without reaching the control values. Blood coagulation inhibitors behaved differently; PC was higher in patients than in controls at all stages (p less than 0.05) whereas ATIII values were significantly decreased at the onset (p less than 0.05), but increased during the course the disease (p less than 0.01). No changes were observed in the D-dimer plasma levels. These data suggest that the thrombotic risk in nephrotic syndrome is particularly evident at the onset of the disease, and appears to be due mainly to changes in platelet number and function, and to increased fibrinogen levels rather than to alterations of plasma anticoagulant factors.

Processing of a polycistronic mRNA requires a 5' cis element and active translation. We have characterized a major processed species of mRNA in the his operon of Salmonella typhimurium. In vivo and in vitro analyses of the his transcripts from wild-type and mutant strains using S1 nuclease protection assays, measurements of RNA stability, deletion mapping, gel retardation, and in vitro translation assays demonstrate that the distal portion of the polycistronic his mRNA is processed, resulting in increased stability. The processing event requires an upstream cis-acting element and translation of the cistron immediately downstream of the 5' end of the processed species. The cistrons contained in this segment are also independently transcribed from an internal promoter which is maximally active in the absence of readthrough transcription from the primary promoter.

A cDNA encoding feline CD4 has a unique repeat sequence downstream of the V-like region. We have cloned, sequenced and expressed a cDNA encoding the feline CD4 glycoprotein. This clone, termed FT121, contains a unique repeat sequence downstream of the V-like region which has not been reported in other mammalian CD4 cDNA. In addition, the cysteine residues at positions 45 and 175 have an unusual pattern. On the other hand, regions other than the unique sequence share significant homology with human CD4 and mouse L3T4 cDNA in the amino acid sequence deduced from the nucleotide sequence, especially in the putative cytoplasmic region. Here, we show that FT121 has a complete open reading frame and efficiently expresses feline CD4 molecules on COS cells. Further we found that the cytoplasmic components, lymphocyte-specific protein-tyrosine kinase p56lck binding sites and phosphorylation site (serine resides), are well conserved, though the extracellular region of the feline CD4 molecule deduced from FT121 is probably different from that of human CD4 and mouse L3T4.

Plasma histamine changes during provoked bronchospasm in asthmatic patients. Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.

Sulfate and galactose metabolism in differentiating ciliary body and iris epithelia: autoradiographic and ultrastructural studies. Immature and adult rat eyes were bisected and incubated with 35-SO4 and 3-U-galactose in short-term pulse-chase experiments. Autoradiographs (ARG) of the tissue revealed that very little sulfate is incorporated by the peripheral neural retina, the pigment epithelia of the retina, ciliary body, or iris. The inner, inverted optic cup cells at the ora serrata, i.e., those that are undergoing differentiation into the unpigmented epithelium of the ciliary body, incorporate large amounts of 35-sulfate into "fixable" macromolecules. The sulfate label is chased from the apically located Golgi apparatus to the basal surface of these cells within one hour. Ultrastructurally, these cells are beginning to develop lateral and basal invaginations of the plasma membrane characteristic of the adult secretory epithelial cells. Electron microscopic ARG show label associated with the plasma membranes. The sulfated macro-molecules at this site appear to be glycolipids and glycoproteins rather than glycosaminoglycans. The preferential synthesis of these macromolecules and their placement at the cellular site of aqueous humor production suggests a role for these sulfated substances in establishing, and perhaps maintaining, that secretory process. 3-H-galactose was incorporated into "fixable" macromolecules to some degree by all the neuroepithelial cells. After chase incubation, ARG showed a high concentration of label in differentiated retinal pigment epithelium (RPE), but not in undiffenentiated peripheral RPE. Ciliary body unpigmented and pigment epithelium, and iris muscle cells incorporate galactose, but to a lesser degree than either RPE or corneal endothelial cells.