Datasets:

9rofe

/

pubmed_reading_levels

like 0

An analysis of the pattern of facial injuries in a general accident department. Over a period of one year 20 549 new patients attended an accident and emergency department. Of these patients, 15 555 were victims of accidents, including 875 who had sustained facial injuries. This latter group comprised 609 patients with soft tissue trauma and 266 with skeletal injury. The frequency, aetiology, age and sex distribution of the facial injuries were analysed and compared with other published statistical surveys of facial injury. It is concluded that facial injuries constitute a significant proportion of the work of a civilian accident unit and that any accident service must have adequate facilities for the management of these injuries.

[Detection of point mutation of Kirsten ras oncogene in pancreatic carcinoma by polymerase chain reaction]. Regarding to the pancreatic cancer, outcomes of the patients surgically treated have been poor. By using polymerase chain reaction (PCR), paraffin-embedded specimens of the pancreatic carcinoma were confined point mutation in Kirsten (K)-ras codon 12. Then, incidence and type of point mutation of this oncogene and correlative studies with stage, T or N factor of pancreatic cancer were analysed. Extremely high incidence of K-ras gene mutation was shown in present report. The highest mode of point mutation of K-ras oncogene was GGT to GAT coded aspartic acid. Cases without point mutation in K-ras codon 12 were significantly frequent in papillary adenocarcinoma than in tubular type. There were not correlative result among mutation types, stage and T factor of pancreatic cancer. Most patients with pancreatic cancer who survived more than 2 years have not shown mutation to aspartic acid. Four cases including two cases of mucin producing pancreatic cancer did not have point mutation in K-ras codon 12. Pathogenesis of mucin producing cancer can be distinguished from typical pancreatic cancer by detection of point mutation in K-ras codon 12 using PCR.

Effect of sequential early burn wound excision and closure on postburn oxygen consumption. To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.

Transcapillary escape rate of albumin and right atrial pressure in chronic congestive heart failure before and after treatment. The transcapillary escape rate of albumin (TERalb), i.e., the fraction of intravascular mass of albumin that passes to the extravascular space per unit of time, was determined from the disappearance of intravenously injected 125I-labeled human serum albumin during the first 60 minutes after injection in 10 subjects with chronic right heart failure. The investigation was repeated after sodium and water depletion. Before treatment TERalb was significantly elevated (mean 8.3 +/- 1.6% (SD)/hour, in comparison to values for normal subjects (mean 5.4 +/- 1.1%/hour, P less than 0.001). With treatment TERalb decreased significantly (mean 5.9 +/- 1.2%/hour, P less than 0.01). Right atrial pressure decreased from an average of 10 mm Hg to 6 mm Hg during treatment. A statistically significant, positive correlation was found between TERalb and right atrial pressure (r = 0.77, P less than 0.001). Our results best can be explained by increased filtration, mainly through the venous end of the microvasculature, due to the increased venous pressure in heart failure.

Altered interleukin-1 production in mice exposed to rotation stress. This study examined the effects of rotation stress (78 circles per 1 min for 1 h: 10 min rotation + 5 min interval) on peritoneal macrophage release of lymphocyte-activating factors (LAF) and interleukin-1 alpha (IL-1 alpha) concentration in mice (CBA x C57BL6)F1. Rotation stress induced the macrophages' release of LAF with peak reactions in 0-1 h after termination of stress, followed by elevation of plasma IL-1 alpha. Induction of LAF release was accompanied by a higher concentration of corticosterone (Cs) in the blood, most prominent at 0 and 0.5 h after termination of the stressful procedure, and recovering to normal values 1 h later. It is suggested that the stimulating effect of stress on LAF and IL-1 production possibly involves glucocorticoid hormones, as well as other stress-induced neurohumoral shifts accompanying the reaction of glucocorticoids. It is also possible that the activated production of LAF and IL-1 by macrophages has a stress-limiting role in cases of mild stress.

Inhibition of acoustic priming in mice. Mice of the C57BL/6J strain can be made susceptible to audiogenic seizures by a process known as acoustic priming. Acoustic priming can be blocked when the animals are injected either with puromycin or with puromycin aminonucleoside before the application of the priming stimulus. Cycloheximide, diphenylhydantoin, and d-amphetamine had little effect on priming-induced audiogenic seizures in these animals. All of these drugs, however, when given in combination with puromycin reversed in the protective action of puromycin against audiogenic seizures. Puromycin administered to 19-day-old mice increased susceptibility to electroconvulsive seizures when the animals were tested at 22 days of age. It is suggested that puromycin is able to block priming-induced audiogenic seizures by producing abnormal electrical activity in the brain or through an interference with normal neurohumoral transmission by incomplete peptides.

Recombinant DNA probe detecting Eperythrozoon suis in swine blood. A genomic library to Eperythrozoon suis DNA was constructed in lambda gt11, and from this library, E suis clone KSU-2 was identified as a potential diagnostic probe. In hybridization experiments that used 100-microliters samples of blood collected in chaotropic salt solutions, the KSU-2 probe hybridized strongly with purified E suis organisms and blood samples from splenectomized swine that were parasitized with E suis. However, the probe under stringent conditions did not give radiographic indications of hybridizing with equine blood DNA, bovine blood DNA infected with Anaplasma marginale, canine blood DNA infected with Ehrlichia canis, feline blood DNA infected with Haemobartonella felis, or uninfected swine blood DNA.

Final results of a dental caries clinical trial using heat killed lactic bacteria (Streptococci and Lactobacilli) orally. The results of a dental caries clinical trial in 245 seven-year-old children are reported. Chewable tablets of two different types were prepared: A) Containing pyridoxine (Vit. B6) and heat-killed lactic bacteria. B) Placebo tablets with pyridoxine only. They were randomly given once a week for 16 weeks to experimental and control groups respectively. Four evaluation surveys were conducted during 24 months of follow up, using the "Decay, Missing, Filled, Surfaces" index (DMFS) for the clinical evaluation of the permanent teeth. A consistent reduction in the incidence of dental caries in the experimental group was observed in all 4 surveys. After 2 years of follow up a 42% reduction in the incidence rate of dental caries was observed in the experimental group compared to the control group. Summary tables and discussion of the clinical evaluation surveys are given. The potential use of these clinical findings as support for a future dental caries vaccine evaluation project is proposed.

Hernia in northern Jordan. Some epidemiological considerations. This retrospective study covers the authors' experience over five years of 1,722 primary hernia repairs in 1,722 patients of all ages. An analysis of some epidemiological features is presented and discussed. Inguinal hernia was by far the commonest variety accounting for more than 84% of the total series. Regardless of sex and type of hernia, 60% of all hernias were right-sided while not more than 5% were bilateral. The male to female ratio for the entire series was 4.3:1 and 8.2:1 for the inguinal hernia group. The main findings of this retrospective study are in direct accord with other series reported in the literature. Furthermore, we suspect our results are typical of those to be found in large and comparable general community hospitals in Jordan.

Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate. Previous studies of risk factors for acute graft-versus-host disease (GVHD) involved patients receiving predominantly single-agent prophylaxis. Therefore, a retrospective analysis was performed on 446 patients, from a single institution, who received transplants of marrow from HLA-identical siblings and the combination of cyclosporine (CSP) and methotrexate (MTX) to determine risk factors for acute GVHD associated with this more effective form of GVHD prophylaxis. The incidences of Grades II-IV and Grades III-IV (severe) acute GVHD were 35% and 16%, respectively. Increased clinical grades of acute GVHD in patients without advanced malignant disease were associated with a decreased survival. In a multivariate Cox regression analysis, risk factors associated with the onset of Grades II-IV acute GVHD were sex mismatch and donor parity (P = .001), increased dose of total body irradiation (TBI) (P = .001), and reduction to less than 80% of the scheduled dose of MTX (P = .02) or CSP (P = .02). The multivariate analysis indicated a relative risk of 1.37 for acute GVHD in a group defined as having advanced malignant disease at transplant; however, this difference failed to reach conventional levels of statistical significance (P = .07). Reduction of MTX and CSP occurred in up to 36% and 44% of patients, respectively, primarily because of renal or hepatic dysfunction. The periods of increased risk for the onset of acute GVHD were up to 1 week after a reduction of MTX and 2 weeks after a reduction in CSP. When only patients who developed Grades II-IV acute GVHD were considered, the more severe acute GVHD of Grades III-IV was associated with increased patient age of 40 years or greater (P = .05) and dose reductions of CSP (P = .008). Serologic status of patient and donor for cytomegalovirus (CMV), HLA antigens in the A and B loci, and isolation in a laminar air flow room during marrow transplantation, all previously identified as risk factors for acute GVHD, were not confirmed as risk factors in this study population. The toxicity of MTX and CSP and the development of acute GVHD from inadequate immunosuppression because of dose reduction warrants further trials with potentially less toxic immunosuppressive agents. Risk factors for acute GVHD should be considered in clinical management and in the design of clinical trials.

Vascular transformation of lymph node sinuses. A process displaying a spectrum of histologic features. Nonneoplastic vascular lesions in lymph nodes have been infrequently reported. These lesions are believed to be rare and display histologic features ranging from minimal changes associated with vasodilation to vascular proliferative lesions resembling Kaposi's sarcoma. The spectrum of histologic features observed in these cases appears to be the result of the extent and duration of regional lymphatic and/or venous obstruction. We describe two such cases, one presenting in a 66-year-old black woman, after undergoing radical mastectomy for treatment of invasive ductal carcinoma of the breast following a breast biopsy; the other presenting in a 66-year-old black man with obstruction of the subclavian vein. We consider these cases worthy of review, both from a diagnostic standpoint and in the differential diagnosis of vascular neoplasms of lymph nodes, especially Kaposi's sarcoma.

[Radiosensitization with metronidazole. Pharmacocinetical comparison by means of blood level curves after administration of "metronidazol" in the form of tablets, suppositories, and enemas (author's transl)]. Severe acute gastrointestinal side-effects following high oral doses of metronidazole (6 g/m2) could be avoided by a combined oral and rectal application. With tablets and an enema (1 g metronidazole/2 ml) in a ratio 1:4 and an increased dosage of 10 g/m2, maximal serum concentrations of about 200 micrograms/ml are obtained like after an oral dosage of 6 g/m2. The maximal radiosensitizing effect on hypoxic tumor cells is seen five hours after oral application and seven hours after the combined oro-rectal application. No longterm toxicity was found following six high doses of metronidazole.

Properties and separation of T lymphocyte growth stimulatory activity (TL-GSA) and of granulocyte-macrophage colony stimulatory activity (GM-CSA) produced separately from two human T lymphocyte subpopulations. We have previously identified two stimulatory activities affecting blood cell maturation in PHA-stimulated human lymphocytes conditioned medium (PHA-LyCM). One was granulocyte-macrophage colony stimulatory activity (GM-CSA), and the other was T lymphocyte growth stimulatory activity (TL-GSA) in suspension culture. In this paper we have shown that although both activities can be produced from purified non-adherent human T lymphocytes, they are produced from two distinct subpopulations. The production of these activities was greatly enhanced by T cell mitogens. Both protein factors were relatively heat stable (56 degrees, 30 minutes), were sensitive to trypsin treatment and were specific for primate blood cells. These two activities were fractionated by means of ammonium sulfate precipitation, Sephadex G-150 gel filtration, DEAE cellulose and Con A-Sepharose column chromatographies. MW of the major peak estimated from the elution volume of gel filtration in the presence of 0.5 M NaCl was 40,000 for GM-CSA and 13,000 for TL-GSA. Results from Con A-Sepharose column showed that while about 70% of TL-GSA was bound to Con A, less than 25% of GM-CSA was bound. These observations show that the majority of TL-GSA and GM-CSA were separable by these two conventional column chromatographic methods.

Immunolocalization of ecto-5'-nucleotidase in the kidney by a monoclonal antibody. A monoclonal antibody IgG, has been raised against ecto-5'-nucleotidase purified from rat kidney homogenate. The specificity of the antibody was verified by immunoprecipitation. The distribution of the corresponding antigen in the rat kidney was studied by immunocytochemistry (FITC and PAP technique) in 1 micron thick cryostat sections. The antibody reacted with the brush border of proximal tubules, the apical cell membrane and the apical cytoplasm of intercalated cells in connecting tubules and collecting ducts and with interstitial cells of the cortex. Among the interstitial cells exclusively stellate shaped fibroblasts were reactive whereas rounded interstitial cells (type II interstitial cells) as well as pericytes and endothelial cells of peritubular capillaries were unreactive. Compared to the staining intensity of the fibroblasts in the cortical labyrinth the reactivity of the fibroblasts in the medullary rays of the cortex was weak or absent. Interstitial cells of the entire medulla were unreactive. Concerning the fibroblasts in the periarterial connective tissue, those surrounding the larger arteries (arcuate arteries, cortical radial arteries) were negative, those alongside afferent and efferent arterioles were positive. Endothelia of lymphatic capillaries travelling within the periarterial connective tissue were also positive. All components of the juxtaglomerular apparatus were negative. The findings are consistent with an interstitial production of adenosine, available extracellularly and thus being able to reach the major target sites of adenosine, the smooth muscles of glomerular arterioles, including the granular cells at the glomerular vascular pole.

Effects of dietary saturated and trans fatty acids on cholesteryl ester synthesis and hydrolysis in the testes of rats. Studies were made of the enzymic synthesis and hydrolysis of cholesteryl esters in rat testes. Weanling rats were fed for 14 weeks diets containing 5% by wt of hydrogenated coconut oil (HCO), a concentrate of ethyl elaidate and linolelaidate (TRANS), devoid of essential fatty acids (EFA), or safflower oil (SAFF). Cholesterol esterifying activity was localized in the soluble fraction, and cholesteryl ester hydrolase activity was distributed in both particulate and soluble fractions obtained from tissue homogenates. The optimum pH was 6.0 for esterification and 6.9-7.0 for hydrolysis. Neither esterifying nor hydrolytic activity was affected by freezing and thawing, but both reactions were inhibited by heat or sonication. The animals of both the HCO and TRANS groups had developed an EFA deficiency before they were sacrificed. The EFA deficiency produced upon feeding the HCO diet had no apparent effect on the synthesis and hydrolysis of cholesteryl esters in rat testes. The TRANS diet influenced the development of the testes as judged by their size, and cholesterol esterifying and cholesteryl ester hydrolyzing activities were suppressed in the testes of the animals of this group. A major difference in the effects of the HCO and TRANS diets on the lipids of the tests was the relatively minor amount of eicosatrienoic acid (20:3) and the elevated level of docosapentaenoic acid (22:5) in the cholesteryl esters of the testicular lipids of the TRANS group.

The fate of extracellular glutathione in the rat. When intravenously administered to rats, [U-14C]glycine-labelled GSSG, GSH and its analogue ophthalmic acid were rapidly removed from the blood. In perfusion studies with isolated liver, however, the compounds did not enter the liver tissue. Thus, uptake by this tissue is obviously not responsible for the removal of gamma-glutamyl tripeptides from the blood. Instead, rapid hydrolysis of the tripeptides was observed. The undegraded tripeptides were only detected in the blood immediately after administration. Within tissue the degradation product glycine accounted for all the radioactivity. After intravenous injection of the labelled tripeptides the radioactivity accumulated first in the kidney, as shown by autoradiographic studies and chemical analysis of different tissues. The hydrolysis of the gamma-glutamyl tripeptides decreased markedly after the renal arteries were clamped. These observations strongly suggest that renal tissue is the principal site of the degradation of the tripeptides. Inhibition studies and experiments with isolated renal tubules revealed that gamma-glutamyl transpeptidase catalyses the fast hydrolysis of the extracellular peptides. The results indicate that, when entering the extracellular space, glutathione and its analogues are completely hydrolysed and must be resynthesized after reuptake of the constituent amino acids. It is concluded that the degradation occurs mainly on the luminal surface of the renal brush-border membrane and that gamma-glutamyl transpeptidase is a glutathionase acting on extracellular glutathione.

Praziquantel did not exhibit hepatotoxicity in a study with isolated hepatocytes. The effect of praziquantel in different concentrations on isolated rat hepatocytes as a cellular target was studied to detect any possible toxicity. Leakage of cytosolic enzymes, aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase (LDH) was monitored after one hour of incubation of all the cells with the drug. Levels of reduced glutathione (GSH) and cytochrome P450 were also assayed. The drug, in concentrations of 5, 25, 50 and 100 micrograms/ml, had no effect on any of these parameters. In contrast, the hepatotoxic compound trichloroethylene showed dose-dependent toxicity, as measured by trypan blue (TB) exclusion, LDH leakage, and reduction in GSH content in the present cellular model. These results suggest that praziquantel is a relatively safe drug with respect to liver function.

Negligible and non-negligible risks in radiodiagnostic examination of patients. Ionizing radiation is regarded as a health hazard, but one is prepared to neglect this factor on the basis of certain motives. In 1975, KNOX published an analysis of these motives, none of which proved tenable. He concluded that a situation which in daily usage is described as safe, is one which entails risks considered to be negligible so that no safety measures are taken. It can be empirically established that in various health-endangering situations a health hazard of less than 1 X 10(-5) is being neglected. This article studies the risk factors to the individual patient in radiodiagnostic examinations involving low, medium and high radiation exposures. The estimates show that radiohygenic measures on behalf of the patient are advisable.

[A biliary endocrine cell carcinoma: a report of two cases]. An endocrine cell carcinoma is a carcinoid tumor that has an especially malignant prognosis. We herein report on 2 cases of a biliary endocrine cell carcinoma. Case 1 involved a 68 year old man manifesting a fever, jaundice, hepatomegaly and a ballooned gallbladder. After decreasing the jaundice by PTCD, an exploratory abdominal operation was performed. As a tumor was found at the papilla of Vater, a pancreaticoduodenectomy was done. Case 2 involved a 72 year old woman who was diagnosed as having a gallbladder tumor and cholelithiasis. She was given a cholecystectomy and a choledocholithotomy. These 2 cases had hepatic metastasis within a year and subsequently died. Procedurally, an endocrine cell carcinoma should be treated separately from classical carcinoid tumors.

Establishment and characterization of two cell lines derived from human glioblastoma multiforme. We established and characterized two cell lines derived from glioblastoma multiforme. Both cell lines exhibited tumor cell morphology and growth kinetics and showed variable expression of glial fibrillary acidic protein (GFAP), S-100, fibronectin and vimentin. Cytofluorimetrical analysis of tumor samples showed a diploid DNA distribution, whereas permanent culture cells evolved to the hyperdiploid DNA content. Karyotype studies revealed cytogenetical abnormalities described in glial tumors including gain of chromosome 7, loss of chromosome 10 and presence of double minutes (DMs). Enhanced expression of Ha-ras and c-myc genes resulted from high p-21 and p-62 levels. The contemporary presence of TGF-alpha and EGF-Rc transcripts suggested an autocrine mechanism in the cell lines growth.

Sequential activation of genes for heme pathway enzymes during erythroid differentiation of mouse Friend virus-transformed erythroleukemia cells. Changes in the level of transcripts encoding enzymes of the heme biosynthetic pathway as well as those encoding ubiquitous proteins were examined in murine Friend virus-transformed erythroleukemia cells during erythroid cell differentiation induced by chemicals including dimethyl sulfoxide (DMSO). Early changes following DMSO treatment were marked decreases in mRNAs for three ubiquitous proteins, i.e., a 70 kDa heat shock protein (less than 6 h), heme oxygenase and nonspecific delta-aminolevulinate synthase (ALAS) (less than 12 h). These changes were followed by sequential increases in mRNAs for enzymes in the heme biosynthetic pathway. Namely, mRNAs for the erythroid-specific ALAS, delta-aminolevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase started to increase at 12, 18, 18-24 and 24 h, respectively. Nuclear runoff studies revealed that these changes are largely transcriptional. Treatments with other inducers of erythroid differentiation, e.g., hexamethylene bisacetamide, n-butyric acid and N'-methylnicotinamide, also showed similar effects on mRNAs as those following DMSO. These findings suggest that both suppression of ubiquitous genes and activation of heme pathway enzyme genes are associated with erythroid differentiation, and the former occurs preceding changes in the latter.

5-Hydroxytryptamine1A receptor agonists in animal models of depression and anxiety. The effects of different doses of buspirone, 3-dipropyl-amino-5-hydrochromar (NDO 008) and 8-hydroxydipropyl-aminotetralin (8-OH-DPAT) (administered intraperitoneally) were studied in tests of anxiolytic and antidepressant action in rats. These tests included the elavated plus maze test, the forced swim test, stress-induced suppression of open-field behavior, and the differential-reinforcement-of-low-rates-of-behaviour-72 sec (DRL 72 s) test. Buspirone (0.125 mg/kg) and NDO 008 (1.0 to 2.0 mg/kg) produced anxiolytic activity in the elevated plus maze, whereas 8-OH-DPAT did not in the doses employed. All three compounds increased activity in the forced swim test, although buspirone did so at a lower dose than NDO 008 and 8-OH-DPAT. In the stress-induced suppression test of open field activity all three compounds induced an antidepressant-like effect at different doses dependent on whether footshock (stressor) was presented 24 hr before or just prior to the open-field test. All three compounds even caused some reduction of activity in the non-shocked rats. 8-OH-DPAT (1.0 mg/kg) produced a significant and reliable increase in the Reinforcement/Response rate quotient in the DRL 72s test. These diverse results may provide an indication of potential clinical efficacy of the 5-HT1A agonists in the treatment of anxiety and depression.

Computed tomographic localization for fine needle aspiration biopsy of orbital tumors. Fine needle aspiration biopsy techniques have recently been applied to the evaluation of orbital masses. Ultrasound and CT examination have been useful in accurately localizing and characterizing such lesions prior to biopsy. Small retrobulbar tumors may be difficult to biopsy using blind needling, despite accurate localization. Preliminary studies on cadaver orbits confirmed that successful biopsy of the normal optic nerve could be accomplished using direct CT guidance. The technique was applied to 2 patients with monocular blindness due to small infiltrating optic nerve tumors and a histologic diagnosis was obtained in each case. This low morbidity procedure though applicable to only a small group of patients may spare them the morbidity of an orbitiotomy or craniotomy.

Characterization of a 130,000-dalton glycoprotein isolated from pulmonary secretions of patients with alveolar proteinosis. A new glycoprotein with an apparent molecular weight of 130,000 was isolated, purified, and partially characterized from the pulmonary secretions which accumulate so massively in the lungs of patients suffering from pulmonary alveolar proteinosis. The amino acid analysis of the glycoprotein showed the presence of relatively high amounts of glycine, glutamic acid, aspartic acid, leucine, and valine, and small amounts of hydroxyproline, but no hydroxylysine. It contains approximately 6% hexose, 3% sialic acid, and 4% glucosamine. The neutral sugars are galactose, mannose, and fucose. This alveolar glycoprotein cross-reacted with an antiserum prepared in rabbits against a larger glycoprotein (250,000 mol wt) isolated from the same source, suggesting that the larger alveolar glycoprotein may be the precursor of the smaller one.

Studies in neuronal ceroid-lipofuscinosis: leukocyte peroxidase deficiency in a patient with neuronal ceroid-lipofuscinosis (Jansky-Bielschowsky type). Leukocyte peroxidase deficiency has been demonstrated in a confirmed case of neuronal ceroid-lipofuscinosis with guaiacol, o-dianisidine, and p-phenylenediamine used as hydrogen donors in the peroxidase assay system. Nitroblue tetrazolium (NBT) reduction values in the leukocytes of the patient were also found to be significantly higher than those of normal controls, indicating the impaired hydrogen peroxide catabolism. When the patient was given a daily dose of vitamin E (400 I.U.), vitamin C (1 gm), and methionine (1 gm.) along with a weekly intramuscular injection of vitamin B12, the leukocyte peroxidase values of the patient returned to normal levels in about 7 weeks. NBT reductions values also decreased to normal levels. The regenerated enzyme in the patient's leukocytes was shown to have similar chromatographic and electrophoretic properties as the leukocyte peroxidase of normal controls. After about 28 weeks of therapy, the peroxidase levels in the leukocytes of the patient returned to original low levels, with concomitant increase in the NBT reduction values. The effect of vitamin therapy on normal control subjects was, at least in some cases, an increase of leukocyte peroxidase. A significant increase in the peroxidase levels of the patient's leukocytes during vitamin therapy remains unexplained, and the possibility of peroxidase deficiency being a secondary manifestation rather than the primary defect in Batten's disease cannot be ruled out.

[Gastro-intestinal involvement in non Hodgkin's lymphomas, 31 cases (author's transl)]. Gastro-intestinal involvement is a distinctive feature of non-Hodgkin's lymphomas. 31 cases are reported among 200 cases on NHL observed between 1960 and 1976. Multiple involvement appeared in 61%; a diffuse histological pattern is frequent (67%). The relapse of primary isolated gastro-intestinal localization (always) affected extra-digestive tissues (nodes, cavum). Chemotherapy is the mainstay of treatment COP, COAP and MOCA. Surgery is associated in localized involvement or in case of obstruction. High energy radiation therapy is indicated only in lymphosarcomas: -- to residual tumor after chemotherapy--in localized involvement diffuse on all the abdomen at 25 grays after surgery and a brief course of chemotherapy versus surgery and long course of chemotherapy alone.

Long-term benefits of therapy with cyclophosphamide and prednisone in patients with membranous glomerulonephritis and impaired renal function. Long-term follow-up data are provided for a previously reported study of patients with membranous glomerulonephritis (MGN), nephrotic syndrome, and renal function impairment. Nine patients were treated with cyclophosphamide (1 to 2 mg/kg) and six of these received concurrent prednisone; they are compared with 17 concurrent controls (14 of whom had received prednisone at some time). The mean follow-up is 83 +/- 13 months in the treated patients and 64 +/- 7 months in the controls. Of the nine treated patients, four achieved a complete remission from the nephrotic syndrome (proteinuria less than 0.5 g/d), and five a partial remission (proteinuria decreased by at least 50% and to less than 3.5 g/d). One of the nine treated patients and 10 of the 17 controls have reached end-stage renal disease (ESRD) (P less than 0.05). Nine of the controls reaching ESRD had persistent nephrotic syndrome, whereas of the seven controls who have not yet reached ESRD, only two have persistent nephrotic syndrome (chi 2, P less than 0.02). There have been four relapses in three treated patients, and three of the four have responded to repeat therapy. One patient refused full therapy and remains nephrotic. Life-table analysis demonstrates significantly increased survival from ESRD in treated patients as compared with controls (P = 0.04).

Effect of charcoal-broiled beef on antipyrine and theophylline metabolism. Eight healthy volunteers were sequentially fed a control diet, a charcoal-broiled beef--containing diet, and the control diet a second time. The mean plasma half-lives (t1/2) of antipyrine and theophylline were each decreased by 22% after the subjects were fed the charcoal-broiled beed--containing diet. The main plasma t1/2s for these drugs returned to control values when the subjects were fed the control diet for a second time. Considerable individuality occurred in the responsiveness of the subjects to the charcoal-broiled beef--containing diet. The decreases in antipyrine plasma t1/2s among the 8 subjects ranged from 5% to 39%, and the decreases in theophylling t1/2s ranged from 0% to 42%.

[Automated analysis of cardiotocographic signals]. Cardiotocographic signals, used as a perinatal diagnostic tool, comprise fetal heart beat signals (FHR), uterine contractions (UC) and fetal movements (FM). Visual inspection of these three signals is limited, subjective, time consuming and with low reproducibility. The present paper illustrates an application of signal processing techniques to the automatic analysis of cardiotocographic signals, allowing to overcome visual inspection limitations. Porto system of cardiotocograms automatic analysis acquires the signals from a conventional cardiotocograph. The signals are stored and processed by a personal computer. System software allows the user to perform several operations such as signal acquisition, signal storage and retrieval from files, signal analysis and display. Signal analysis is preceded by various signal conditioning operations (filtering, spike removal, etc.) and consists in the estimation of several parameters with diagnostic value: FHR baseline; FHR accelerations and decelerations; uterine contractions; long and short term FHR variability. The system prototype is working on a routine basis at the Obstetrics Department of S. João Hospital (main Oporto Hospital) and is being evaluated using a large data set. A preliminary evaluation performed by 3 experts on a 50 cases set, yielded an agreement rate with computer measurements of 98% for the baseline, 72% to 82% for accelerations and decelerations and 76% for the uterine contractions.

Changes in frying fats with batters containing egg. The effect of whole egg and egg yolk phospholipids in a fritter-type batter on changes in color, phosphorus content, percentage of free fatty acids, and NUAF fatty acid esters of a corn oil and a hydrogenated vegetable shortening used for approximately 7 hr. of frying was studied. A highly significant (P less than 0.01) increase in the percentage of free fatty acids, phosphorus content, and darkening of color in the frying fats was associated with the presence of egg or egg yolk phospholipids in the batters. NUAF fatty acid esters in the frying fats were not significantly affected by the batters being fried. These data support the suggestion that diffusion into the frying fat of phospholipids from fried batters containing egg yolk contributes to an increase in free fatty acids and a darkening of color in the frying fat.

Progressive behavioral changes in rats after exposure to low levels of ionizing radiation in utero. The deleterious effects of ionizing radiation on the developing brain may be not only prolonged but progressive. Fetuses were exposed to 0.75 Gy of ionizing radiation on gestational day 15 through whole body exposure of the pregnant rat. Three behavioral tests (gait analysis, continuous corridor activity and photographic analysis of sequences of behavioral acts) were performed at 1 and 3 months, postnatally. Body weight and thickness of the cerebral cortex of irradiated rats were 10-15 percent below controls throughout the period of study. Behavior in all tests was more affected at 3 months than at 1 month of age. Gait of control rats, as measured by the angle of advanced of hind feet, widened about 20 percent for males and 40 percent for females from 1 to 3 months, as expected, while, in irradiated rats, the angle widened only about 10 percent. Continuous corridor activity increased less than 10 percent in controls and about 35 percent in irradiated rats over the same period. In photographic analysis of behavior, controls increased their time spent standing by about 50 percent in males and 20 percent in females from 1 to 3 months of age. Irradiated males increased time standing only about 10 percent and irradiated females decreased about 30 percent over the same period. The data obtained in these experiments support other evidence that some behavioral alterations from perinatal exposure to radiation become more marked with maturation.

Does intracellular histamine mediate mast cell histamine release? Previously, we demonstrated that through binding a novel intracellular receptor of microM affinity (HIC), histamine mediates, and the HIC antagonist N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine. HCl (DPPE) inhibits, platelet aggregation and serotonin granule secretion; the latter response is dependent upon the same processes that mediate histamine release from mast cell granules. We now show that, as for platelet serotonin release, DPPE blocks concanavalin A-stimulated mast cell histamine release with a potency (IC50 = 30 microM) greater than the H1-antagonist, pyrilamine (IC50 = 150 microM) or the H2-antagonist cimetidine (IC50 = 5 mM), correlating with rank order of potency to inhibit 3H-histamine binding in rat brain membranes and liver microsomes. We postulate that histamine release from mast cells is mediated at HIC by second messenger intracellular histamine. However, unlike platelets, mast cells do not appear to rely on newly synthesized histamine. Rather, as for calcium, histamine may be mobilized from bound stores to mediate histamine secretion.

Measurements of the effective thyroxine ratio (ETR) in the neonate, infant, and child. The applicability of the effective thyroxine ratio (ETR) was assessed in euthyroid neonates, infants, and children. ETR determinations on cord blood fell within the normal adult range. In contrast, ETR values of newborns age 4 hr to 2 days were all elevated (1.17 -1.37) and within the hyperthyroid range for adults. Values in infants age 2 weeks and older and in children age 1-15 years all fell within the normal adult range. These findings suggest that the ETR can be used as an ancillary measure of thyroid function in infants and children. In the immediate postpartum period, however, ETR values may be normally in the adult hyperthyroid range.

The mutagenic modulating effect of p-phenylenediamine on the oxidation of o- or m-phenylenediamine with hydrogen peroxide in the Salmonella test. The mutagenicity of o- and m-phenylenediamine (PD) was remarkedly enhanced by oxidation; their major mutagenic oxidation products were 2,3- and 2,7-diaminophenazine, respectively. In order to evaluate the modulation effect of p-PD on the oxidation of m- or o-PD, p-PD and mixtures of m- and p-PD (m-PD/p-PD) and o- and p-PD (o-PD/p-PD) were oxidized with hydrogen peroxide and their mutagenicity was tested in Salmonella typhimurium TA98 in the presence or absence of a mammalian metabolic activation system (S9 mix). The H2O2-oxidized m-PD/p-PD and o-PD/p-PD were potent mutagens with S9 mix, whereas H2O2-oxidized p-PD was slightly mutagenic. The major mutagenic oxidation products of m-PD/p-PD and o-PD/p-PD were identified as 2,7- and 2,3-diaminophenazine, respectively, by TLC and HPLC. 2,8-Diaminophenazine was also found as a reaction product in oxidized m-PD/p-PD, and it was weakly mutagenic. The mutagenic potency of oxidized m-PD/p-PD or o-PD/p-PD was lower than that of singly oxidized m-PD or o-PD. The yield of 2,7- and 2,3-diaminophenazine was obviously decreased with increases in p-PD, and it was concluded that the declined mutagenic potency of oxidized m-PD/p-PD or o-PD/p-PD was due to the decrease in diaminophenazines. But the formation of diaminophenazines was not completely inhibited by the addition of a 9-fold molar ratio of p-PD to m-PD or o-PD, 8.6 nmole of 2,7-diaminophenazine and 1882.4 nmole of 2,3-diaminophenazine were formed from 1 mmole of m-PD and o-PD, respectively.

A useful cholesterol solvent for medical dissolution of gallstones. Dissolution of cholesterol gallstones by direct instillation of an agent into the biliary tract has been considered an alternate to surgical procedures. We developed an excellent direct solubilizer by combining d-limonene and medium-chain monoglyceride. This mixture enhances the advantages of each individual solvent and minimizes the disadvantages. In vitro experiments were done to determine the viscosities and the cholesterol dissolving rates of various combinations, and in vivo experiments were conducted to study their irritation effects on tissues. The optimal combination was a 3:2 mixture of d-limonene and medium-chain monoglyceride. It could quickly dissolve cholesterol gallstones with minimal or no observable side effect.

Effect of the cardioprotective agent stobadine on reproduction in rats. The cardioprotective drug stobadine in the form of dipalmitate salt DP 1031 was evaluated for its effects on perinatal and postnatal development in the rat. Doses of 5, 15 and 50 mg/kg/day representing approximately 1, 3, and 10 times the anticipated maximum daily human therapeutic dose were administered to rats orally in aqueous suspension. Treatment of pregnant rats with stobadine continuously from day 15 of gestation through parturition and lactation had no adverse effects on reproductive parameters of dams or on survival and development of F1 offspring at any dose used. There were only signs of slight maternal toxicity at 50 mg/kg/day, which consisted of sedated behaviour, reduced liver weight and reversible histopathological changes in kidney tissue. (Tab. 3, Fig. 4, Ref. 24).

The tnpA and tnpD gene products of the Spm element are required for transposition in tobacco. The maize Suppressor-mutator (Spm) element encodes four alternatively spliced transcripts designated tnpA, tnpB, tnpC, and tnpD. tnpA and tnpB are monocistronic, whereas tnpC and tnpD are dicistronic, and the protein-coding sequences of each transcript overlap extensively with those of one or more of the other transcripts. We have analyzed the role of the Spm-encoded gene products in element transposition by using cDNAs with a single open reading frame to (1) complement Spm elements with frameshift mutations and (2) complement each other in a tobacco transposition assay. We report that whereas the tnpA and tnpD gene products are essential for transposition, the tnpB and tnpC gene products are not. We have analyzed the structure of empty donor sites, new insertion sites, and potential transposition intermediates. We discuss the implications of our findings for the mechanism of Spm transposition.

Cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma. In order to estimate the possibility of a cytologic differential diagnosis of bronchiolo-alveolar carcinoma and bronchogenic adenocarcinoma, 121 histologically proven cases of these two types of lung cancer were studied. Certain features of the tumor cells were used as differential diagnostic parameters. By means of these features it was possible to correctly type 90% of the bronchiolo-alveolar carcinomas and 72% of the bronchogenic adenocarcinomas. The most striking characteristics of bronchiolo-alveolar carcinoma was the uniformity of cells, the occurrence of such cells in tightly packed clusters, the absence of prominent nucleoli and also the scarcity of single tumor cells. Thus, it seems possible to make a correct cytologic differential diagnosis between these two types of lung tumors with high accuracy.

Ca2(+)-evoked [3H]dopamine release from synaptosomes is dependent on neuronal type Ca2+ channels and is not mediated by acetylcholine, glutamate or aspartate release. Elevation of potassium concentrations ([K+]) in the presence of Ca2+ is the most common method of evoking neurotransmitter release from synaptosomes. However, we have been investigating a method of releasing dopamine from synaptosomes that does not involve using elevated [K+]. In this paradigm of neurotransmitter release, dopamine is released from synaptosomes, previously exposed to micromolar or lower [Ca2+], by 1.25 mM Ca2+ in the presence of non-depolarizing [K+] (4.5 mM). The present experiments characterize the Ca2+ channel(s) involved in the Ca2(+)-evoked release of dopamine from synaptosomes, and determine whether the release is mediated by acetylcholine, glutamate or aspartate. omega-Conotoxin (10 nM), which blocks N-, L- and possibly T-type voltage-sensitive Ca2+ channels (VSCC), inhibited the Ca2(+)-evoked [3H]dopamine release from either striatal or olfactory tubercle synaptosomes to less than 50% of control. Neither 1 microM nifedipine nor 1 microM verapamil, which block L-type VSCC, affected Ca2(+)-evoked release. The N- and T-type VSCC blocker neomycin and the nonspecific Ca2+ antagonist, cobalt2+, inhibited release to a greater extent than omega-conotoxin. At 1 mM, both compounds inhibited release to approximately 30% of control. Neither the excitatory neurotransmitter glutamate nor aspartate (2mM) affected 1 microM LY-171555 (a dopamine D2 agonist) inhibition of Ca2(+)-evoked [3H]dopamine release. Also, the glutamate antagonist, glutamic acid diethyl ester, did not affect either Ca2(+)-evoked release or 1 microM LY-171555 inhibition thereof. The nicotinic antagonist hexamethonium (10 microM) and the muscarinic antagonist atropine (1 microM) were also ineffective in inhibiting Ca2(+)-evoked release or LY-171555 inhibition of release.(ABSTRACT TRUNCATED AT 250 WORDS)

20 years or more of follow-up of living kidney donors. The perioperative and long-term risks for living kidney donors are of concern. We have studied donors at the University of Minnesota 20 years or more (mean 23.7) after donation by comparing renal function, blood pressure, and proteinuria in donors with siblings. In 57 donors (mean age 61 [SE 1]), mean serum creatinine is 1.1 (0.01) mg/dl, blood urea nitrogen 17 (0.5) mg/dl, creatinine clearance 82 (2) ml/min, and blood pressure 134 (2)/80 (1) mm Hg. 32% of the donors are taking antihypertensive drugs and 23% have proteinuria. The 65 siblings (mean age 58 [1.3]) do not significantly differ from the donors in any of these variables: 1.1 (0.03) mg/dl, 17 (1.2) mg/dl, 89 (3.3) ml/min, and 130 (3)/80 (1.5) mm Hg, respectively. 44% of the siblings are taking antihypertensives and 22% have proteinuria. To assess perioperative mortality, we surveyed all members of the American Society of Transplant Surgeons about donor mortality at their institutions. We documented 17 perioperative deaths in the USA and Canada after living donation, and estimate mortality to be 0.03%. We conclude that perioperative mortality in the USA and Canada after living-donor nephrectomy is low. In long-term follow-up of our living donors, we found no evidence of progressive renal deterioration or other serious disorders.

Association of folic acid with rat liver microsomes. Shin et al. (Biochim Biophys Acta 444: 794-801, 1976) described the subcellular location of [3H]folic acid after injection into rats. The microsomal fraction of the liver contained relatively large amounts of tracer initially but lower amounts at later times. Because of the heterogeneous nature of the microsomal fraction of the liver we re-examined the nature of the folate binding fraction. The location of injected [3H]folic acid resembled that of the microsomes derived from the plasma membrane, where ultracentrifugal analysis was conducted in the presence and absence of cesium ions. The location of the folate did not resemble that of microsomes derived from the endoplasmic reticulum (ER). One of the marker enzymes of the ER was the vitamin K-dependent carboxylase. A simple method for reducing vitamin K is described.

Structure-activity relationships of pentamidine analogs against Giardia lamblia and correlation of antigiardial activity with DNA-binding affinity. 1,5-Di(4-amidinophenoxy)pentane (pentamidine) and 38 analogs of pentamidine were screened for in vitro activity against the enteric protozoan Giardia lamblia WB (ATCC 30957). All compounds were active against G. lamblia as measured by a [methyl-3H]thymidine incorporation assay. Antigiardial activity varied widely, with 50% inhibitory concentrations (IC50s) ranging from 0.51 +/- 0.13 microM (mean +/- standard deviation) for the most active compound to over 100.0 microM for the least active compounds. The IC50 of the most potent antigiardial agent, 1,3-di(4-amidino-2-methoxyphenoxy)propane compared favorably with the IC50s of the compounds currently used to treat giardiasis, i.e., furazolidone (1.0 +/- 0.03 microM), metronidazole (2.1 +/- 0.80 microM), quinacrine HCl (0.03 +/- 0.02 microM), and tinidazole (0.78 +/- 0.48 microM). A mode of antigiardial activity for these compounds was suggested by the correlation observed between antigiardial activity and the binding of the compounds to calf thymus DNA and poly(dA).poly(dT).

Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells. We determined the affinity and selectivity of binding for 24 compounds: nine antimuscarinics (including some antiparkinson drugs) and 15 neuroleptics (including the atypical compounds clozapine, fluperlapine, melperone, rilapine, risperidone, tenilapine, tiosperone and zotepine) at the five human muscarinic receptor subtypes expressed in Chinese hamster ovary cells. Equilibrium dissociation constants (Kd) were obtained from competitive radioligand binding studies with [3H]quinuclidinyl benzilate and membranal preparations of these cells. As expected, QNB had the highest affinity of the compounds studied at the five receptor subtypes and was not selective (Kd ranged from 0.027-0.088 nM). Benztropine had the next highest affinity of the antimuscarinic compounds and thioridazine had the highest affinity of the neuroleptics. Among the antiparkinson drugs, biperiden was the only one selective for the m1 subtype; and among the neuroleptics, the atypical drug clozapine was also selective for the m1 subtype. This selectivity may explain clozapine's unusual efficacy in refractory schizophrenic patients and its low incidence of extrapyramidal side effects. However, because most other atypical neuroleptics studied lacked high affinity and selectivity at muscarinic receptor subtypes, it is likely that other mechanisms are involved as well.

Intestinal lactase deficiency in Ceylon (Sri Lanka). Lactose tolerance tests (LTT) in 200 normal adult Ceylonese have shown that 145 (72.5%) had a flat LTT, indicating a population prevalence of lactase deficiency of 66.2 to 78.8%. Jejunal lactase estimations in a smaller sample (41) confirmed this. Twelve of 55 subjects (21.8%) with a normal LTT had intestinal symptoms after lactose and intestinal lactase was low in most of them. It is suggested that little lactase is required to elevate the blood sugar but that more may be required to prevent diarrhea. On the other hand, 65.5% had no symptoms despite a flat LTT, and the possible reasons for this are considered.

Urinary excretion of inorganic pyrophosphate by normal subjects and patients with renal calculi in north-western India and the effect of diclofenac sodium upon urinary excretion of pyrophosphate in stone formers. 24 h urinary pyrophosphate excretion was studied in 20 normal healthy subjects and 75 idiopathic stone formers from north-western regions of India. The mean 24-hour urinary excretion of pyrophosphate was significantly low in stone formers (50.67 +/- 2.16 mumol/24 h) as compared to that of normal subjects (71.46 +/- 5.46 mumol/24 h) (p less than 0.01). Diclofenac sodium, a non-steroidal anti-inflammatory agent, was administered 50 mg thrice daily for 1 week to 18 stone formers and 24-hour urinary pyrophosphate excretion was studied before and after drug therapy. The 24-hour urinary excretion of pyrophosphate increased from 54.32 +/- 21.40 to 78.31 +/- 28.03 mumol subsequent to diclofenac sodium therapy (p less than 0.01).

Bromodeoxyuridine labeling and flow cytometric identification of replicating Saccharomyces cerevisiae cells: lengths of cell cycle phases and population variability at specific cell cycle positions. An immunofluorescent staining procedure has been developed to identify, with flow cytometry, replicating cells of Saccharomyces cerevisiae after incorporation of bromodeoxyuridine (BrdUrd) into the DNA. Incorporation of BrdUrd is made possible by using yeast strains with a cloned thymidine kinase gene from the herpes simplex virus. An exposure time of 4 min to BrdUrd results in detectable labeling of the DNA. The BrdUrd/DNA double staining procedure has been optimized and the flow cytometry measurements yield histograms comparable to data typically obtained for mammalian cells. On the basis of the accurate assessment of cell fractions in individual cell cycle phases of the asynchronously growing cell population, the average duration of the cell cycle phases has been evaluated. For a population doubling time of 100 min it was found that cells spend in average 41 min in the replicating phase and 24 min in the G2+M cell cycle period. Assuming that mother cells immediately reenter the S phase after cell division, daughter cells spend 65 min in the G1 cell cycle phase. Together with the single cell fluorescence parameters, the forward-angle light scattering intensity (FALS) has been determined as an indicator of cell size. Comparing different temporal positions within the cell cycle, the determined FALS distributions show the lowest variability at the beginning of the S phase. The developed procedure in combination with multiparameter flow cytometry should be useful for studying the kinetics and regulation of the budding yeast cell cycle.

Induction of congenital hydrocephalus in hamsters with attenuated and natural strains of mumps virus. The abilities of a low-passage strain and of a live, attenuated vaccine strain of mumps virus to induce congenital hydrocephalus in hamsters were tested by intraamniotic inoculation on the 10th day of pregnancy. Examination of term fetuses and neonates, with cytoplasmic inclusions, cytopathic effects, and specific immunofluorescence used as indicators, demonstrated an oronasal portal of entry for both strains. The vaccine strain appeared to be more pathogenic; it spread primarily into the respiratory tract and hence to the central nervous system. Inclusions were observed as long as 21 days after inoculation. Hydrocephalus and ependymal involvement, potentially capable of producing aqueductal stenosis, were observed in 19 of 81 animals studied 11-29 days after inoculation.

Deficient lipoxin synthesis: a novel platelet dysfunction in myeloproliferative disorders with special reference to blastic crisis of chronic myelogenous leukemia. The capacity to convert exogenous leukotriene A4 to lipoxins (LXs) was investigated in platelet suspensions from patients with myeloproliferative disorders (MPD) (n = 22) and healthy control subjects (n = 14). Platelets isolated from the controls produced mainly LXA4, but also 6(S)-LXA4 and the all-trans isomers of lipoxins A4 and B4, as determined by high-performance liquid chromatography and computerized UV spectroscopy. In comparison to control levels, the mean LX synthesis was significantly lower in platelets from the MPD patients (438.7 +/- 62.8 and 157.4 +/- 31.2 pmol LXA4 per 10(9) platelets, respectively; mean +/- SEM; P = .0001). Platelets from six of the patients showed a particularly low capacity to produce LXs, resulting in LX levels below the detection limit or less than 7% of mean control levels. Notably, all these patients were in blastic crisis of chronic myelogenous leukemia (CML). This severely deficient LX production was paralleled by a dramatically attenuated conversion of arachidonic acid to 12-HETE (12-hydroxyheptadecatrienoic acid), a product formed via the prostaglandin endoperoxide synthase pathway, was normal. In addition, longitudinal studies of CML patients showed that blastic metamorphosis was associated with a markedly reduced capability to synthesize LXs, while this capacity improved after retransformation into a second chronic phase. The results reveal deficient LX synthesis as a novel platelet dysfunction in MPD, particularly in blastic crisis of CML in which an essentially abolished 12-lipoxygenase activity may be a general phenomenon.

Familial insulinoma: description of two cases. We describe cases of isolated functioning insulinoma occurring in two members of the same family (father and daughter). The father had a first encapsulated insulinoma diagnosed at 14 years of age and at the age of 33 years he was operated on for a second insulinoma infiltrating the exocrine pancreas with lymph node metastases. The daughter was operated on for an encapsulated insulinoma in the tail of the pancreas when she was 6 years old. No clinical and laboratory signs of other endocrine disturbances have so far been detected in either care or in any other members of the family. Our report suggests the possibility of multiple familial insulinoma, although this is an extremely rare condition. Our data also indicate that insulinomas, even if well controlled by medical treatment, should always be removed by surgery because malignancy cannot be excluded with certainty. Moreover, patients should be closely followed up, as recurrence may develop up to 15 years after surgery.

Comparison of three new nonculture tests in the diagnosis of Chlamydia genital infections. This study compares three new rapid nonculture tests to cell culture with passage for the diagnosis of Chlamydia genital infections in sexually active adolescent and young adult females. Two hundred consecutive patients having a pelvic examination had cervical samples taken for the following: Papanicolaou smear, gonorrhea culture, Chlamydia cell culture, direct fluorescent antibody (DFA; Difco), isotopic DNA probe (Gen-Probe), and enzyme immunoassay (EIA; IDEIA III, Novo BioLabs). After resolution of discrepant results, 25 of the specimens were judged to be positive. The DFA identified 17 of the 25, with 3 false-positive results; the DNA probe identified 20 of the 25, with no false positive results; and the EIA identified 22 of the 25, with one false-positive result. The sensitivities, specificities, and positive and negative predictive values, respectively, were DFA, 68%, 98.2%, 85%, 95.5%; DNA probe, 80%, 100%, 100%, 97.2%; and EIA, 88%, 99.4%, 95.6%, 98.3%. These new rapid nonculture tests are comparable and relatively reliable, with trends favoring the EIA and the DNA probe. Further studies with larger samples are needed to determine their clinical utility.

Determination of a cyclic heptapeptide, a novel fibrinogen receptor antagonist, in human plasma by high-performance liquid chromatography with automated pre-column derivatization, column switching and fluorescence detection. A sensitive high-performance liquid chromatographic (HPLC) assay for the determination of the cyclic heptapeptide Ac-Cs-Asn-Dtc-Amf-Gly-Asp-Cys-OH (Dtc = beta,beta-dimethylthioproline, Amf = p-aminomethylphenylalanine) in human plasma has been developed. The key steps in the assay include: solid-phase extraction of the drug from plasma, chemical derivatization of the primary amino group with naphthalene-2,3-dicarboxyaldehyde in the presence of N-acetyl-D-penicillamine as a nucleophile to form a fluorescent benzo[f]isoindole derivative, and HPLC with column switching to provide the necessary chromatographic separation of the derivative from endogenous plasma components. The assay has been validated in the concentration range 1-10 ng/ml of plasma.

Protein-heme interaction in hemoglobin: evidence from Raman difference spectroscopy. Raman difference spectroscopy measurements on native and chemically modified human deoxyhemoglobins stabilized in either the R or the T quaternary structure revealed frequency differences in the oxidation state marker lines. The differences indicate that the R structure has an effective increase in the electron density of the antibonding pi* orbitals of the porphyrin rings. This increase is explained by a charge transfer interaction between donor orbitals and the pi* orbitals of the porphyrins. The relative amount of charge transferred, which is inferred from the Raman difference measurements, correlates with some but not all factors that influence the energetics of the quaternary structure equilibrium. In addition, the free energy of cooperativity for a variety of ligated proteins follows the same order as that of the degree of charge depletion of the pi* orbitals upon ligation as determined from the frequency of a Raman mode. The proposed electronic interaction between the protein and heme could result in energies large enough to provide a significant contribution to the energetics of hemoglobin cooperativity.

The impact of selective use of dipyridamole-thallium scans and surgical factors on the current morbidity of aortic surgery. Preoperative cardiac testing in patients undergoing vascular surgery remains controversial. We have advocated selective use of dipyridamole-thallium scans based on clinical markers of coronary artery disease before aortic surgery. The present study assessed both the efficacy of this policy and the role of surgical factors in the current morbidity of aortic reconstruction. Two hundred two elective aortic reconstructions (151 abdominal aortic aneurysms, 51 aortoiliac occlusive disease) performed in the period from January 1989 to June 1990 were reviewed. Preoperative dipyridamole-thallium scanning was performed in 29% of all patients, prompting coronary angiograms in 11% and coronary artery bypass grafting/percutaneous transluminal coronary angioplasty in 9% of patients before aortic reconstruction. The overall operative mortality rate was 2%, with one cardiac-related death. Major cardiac (nonfatal myocardial infarction, unstable angina) and pulmonary complications occurred in an additional 4% and 6%, respectively, of patients. Coronary artery disease clinical markers and surgical factors were analyzed with stepwise logistic regression for the prediction of operative mortality rates and major cardiopulmonary complications. Variables retaining significance in predicting postoperative death or cardiopulmonary complications included prolonged (more than 5-hour) operative time (p less than 0.004), operation for aortoiliac occlusive disease (p less than 0.010), and a history of ventricular ectopy (p less than 0.002). Prolonged operative time (p less than 0.006) and the detection of intraoperative myocardial ischemia (p less than 0.030) were predictive of major cardiac complications after univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. It has been shown recently that cyclosporine is largely metabolized by P450IIIA (CYP3A), an enzyme whose catalytic activity varies significantly among patients. To determine whether heterogeneity in P450IIIA activity contributes to interpatient differences in cyclosporine dosing requirements, the oral pharmacokinetics of the drug were determined in 20 stable kidney transplant recipients. P450IIIA activity was then measured in each patient by use of the erythromycin breath test. In the 16 patients who were at steady state, the logarithm of the apparent oral clearance of cyclosporine correlated significantly with the rate of 14CO2 exhaled in breath after intravenous administration of [14C N-methyl]erythromycin (r = 0.55, p = 0.03). No significant correlations existed between apparent oral clearance and age, high-density lipoprotein cholesterol or low-density lipoprotein cholesterol, or hematocrit in these patients. We conclude that heterogeneity in P450IIIA activity significantly contributes to interpatient differences in dosing requirements of cyclosporine in kidney transplant patients.

Phagosome-lysosome interactions in cultured macrophages infected with virulent tubercle bacilli. Reversal of the usual nonfusion pattern and observations on bacterial survival. Tubercle bacilli of the pathogenic human strain H37Rv had previously been shown to multiply, after ingestion by cultured mouse peritoneal macrophages, within phagosomes that tended to remain unfused with secondary lysosomes. Means were sought therefore for promoting experimentally a modification of the host response so as to attain a high level of phagolysosome formation, enabling tests to be made of any effects on the course and outcome of the intracellular infection. This was achieved by exposing viable bacilli to specific rabbit antiserum before their ingestion. Quantitative assessments, using electron microscopy, now showed that a majority of the phagosomes containing intact bacilli had fused with ferritin-labeled lysosomes, and frequently the fusion was massive. Bacterial viability studies established that the serum pretreatment was not itsel bactericidal. In the course of progressive infections with strain H37Rv, monitored by counts both of viable bacterial units and of intracellular acid-fast organisms, no appreciable difference was found between the intracellular growth rates of control and antiserum-treated bacilli. Concurrent electron microscopy showed that bacilli could remain intact and multiply both in phaagolysosomes and in unfused phagosomes, ruling out the possibility of selective growth of antiserum-pretreated bacilli within the minority of phagosomes that remained unfused. It was concluded that "turning on" phagosome-lysosome fusion in normal macrophages did not influence the outcome of infection with virulent M. tuberculosis; lysosome contents manifestly failed to exercise an antibacterial effect on this organism. Nevertheless, the possibility remains that the lysosomes of specific immune macrophages have antituberculous potentiality. In that case the experimental "turning on or off" of fusion could be a decisive factor in the outcome of a virulent challenge. Should it not be, the antibacterial capabilities of immune cells would need to be ascribed to factors other than lysosomal attack, the latter being essentially for disposal of the dead organisms.

Serum cobalamin and folate in the optic neuropathy associated with tobacco smoking. The concentrations of vitamin B12 in the sera from 77 patients diagnosed as suffering from the toxic optic neuropathy associated with tobacco smoking were compared with control levels and with serum folic acid concentrations from the same patients. Of these, 17 patients had associated pernicious anaemia. Serum vitamin B12 levels were significantly lower, whereas the folic acid concentrations showed great variation. Folic acid levels in the serum tended to be high when the vitamin B12 level was low (r = 0.29). The results suggest that the role of folic acid in the genesis of the optic neuropathy is not marked. However persistently low levels of folic acid occurred in one subject and significant clinical improvement resulted only from specific therapy.

[Effect of inhaled environmental pollutants on the mucous membrane of the upper airways]. Diseases of the mucosa of the upper respiratory tract have increased in the last few decades. In epidemiological studies, an increase in the rate of allergies has especially been noticed. The offensive particles from the environment meet human organism in the respiratory mucosa of the nose: the function of the mucosa depends partly on the protective function of the mucus, ciliae and swelling bodies of the mucosa and partly on the abundant number of immunocompetent effector cells in the subepithelial lamina propria. Of central interest are the mast cells, which initiate reactions by means of the exocytosis of mediators: the hyperergic, anaphylactic reaction and the hyper-reflectoric, anaphylactoid reaction. Environmental noxious agents (sulfur dioxide, nitrous oxides, ozone, carbohydrides and dust particles) influence in different ways the pathological reactions of the mucosa: they provoke inflammatory reactions through toxic and chemical-irritative effects. They lead to the initiation and perpetuation of allergies. This happens through the changing spectrum of allergen exposition, through direct changing of the surface and structure of proteins of the allergens and through the strengthening of the humoral and cellular mechanisms, which are part of the initiation and perpetuation of allergies. Environmental noxious agents initiate hyper-reflectoric reactions of the mucosa, which seems to be the most impressive factor causing the change in rhinological diseases nowadays. Environmental noxious agents are partially responsible for the "priming effects."

Structural differences among guinea pig Fc gamma 1/gamma 2 receptors on macrophages, polymorphonuclear cells, and lymphocytes. Using the cDNA, D-3, coding for Fc gamma 1/gamma 2 receptor of guinea pig macrophages that binds IgG1 and IgG2 (Fc gamma 1/gamma 2R), we examined the cell distribution of this receptor by RNA blot analysis. The Fc gamma 1/gamma 2R mRNA was expressed in polymorphonuclear cells and B cells as well as in macrophages, but not at the detectable level in T cells. The cDNA amplified from RNA of polymorphonuclear cells in the polymerase chain reaction was the same as D-3. The cDNA of B cells was found to have about 140 bp cDNA segment inserted to the cytoplasmic tail of D-3. We found that the cDNA amplified from T cell RNA differed in signal peptide and extracellular domain sequence from cDNAs of other cell types. This cDNA does not seem to be amplified from the mRNAs of contaminating other cell types.

Factors influencing triacylglycerol synthesis in permeabilized rat hepatocytes. Rat hepatocytes were treated with Staphylococcus aureus alpha-toxin to permeabilize their plasma membrane for low-molecular-mass compounds. During incubation with 1 mM labelled fatty acid, phosphatidate and, less clearly, lysophosphatidate rapidly reached a steady state, whereas labelled diacylglycerol accumulated to some extent, at least in the absence of exogenous CDP-choline. Esterification and oxidation were linearly related to the fatty acid concentration, and there was no indication for saturation with acyl-CoA. However, when permeabilized cells were incubated with labelled sn-glycerol 3-phosphate and 1 mM unlabelled fatty acid, glycerolipid synthesis and the level of esterification intermediates reached a plateau between 0.25 and 0.50 mumol of the triose phosphate/ml. The synthesis of phosphatidylcholine was dependent on addition of CDP-choline. In presence of the latter, diacylglycerol no longer accumulated and triacylglycerol synthesis was suppressed, although the sum of synthesized diacylglycerol, triacylglycerol and phosphatidylcholine remained constant. This indicates that the same pool of diacylglycerol is shared by choline-phosphotransferase and diacylglycerol acyltransferase and that the relative activity of these enzymes depends on the CDP-choline supply. Comparison of the levels of the esterification intermediates with the activity of the respective steps of the pathway reveals that, at a fixed fatty acid concentration, glycerophosphate acyltransferase determines the esterification rate, whereas lysophosphatidate acyltransferase and, at low CDP-choline levels, diacylglycerol acyltransferase approach saturation at elevated sn-glycerol 3-phosphate concentration. There is, however, no indication for a regulatory role of phosphatidate phosphohydrolase in this system. The significance of these findings for the regulation of triacylglycerol synthesis under conditions in vivo is discussed.

Axonal transport of [3H]serotonin in an identified neuron of Aplysia californica. A population of characteristic ellipsoidal dense-core vesicles was identified in axons of the giant cerebral neuron of the mollusc Aplysia. We injected [3H]serotonin into the cell body of this identified serotonergic neuron in the isolated central nervous system in order to study the subcellular components associated with the neurotransmitter. Subcellular fractionation by differential centrifugation indicated that injected serotonin was rapidly taken up into particulate form. [3H]Serotonin appeared in the axons within 2 h after injection, and export continued at a constant rate of 6% of the total in the neuron/h thereafter. The dependence of the total amounts of [3H]serotonin which appeared in the axons in 6 h (export from the cell body) on the amounts injected was consistent with the idea that export is a saturable process, possibly depending on the capacity of somatic vesicles or of some unidentified carrier for serotonin. [3H]Serotonin moved into both major branches of the axon, where it was translocated rapidly. The transmitter, which was shown by autoradiography to be restricted to the axons of the injected cell, was distributed along axons in accumulations of radioactivity; in contrast, its precursor, [5-3H]hydroxytryptophan, moved slowly along axons in a smooth, declining curve, its kinetics consistent with diffusion. Quantitative electron microscope autoradiography revealed that the dense-core vesicles and the cytosol of axons fixed with glutaraldehyde were labeled with [3H]serotonin.

[In vivo anti-tumour efficacy of tumour necrosis factor and interferon- alpha, -gamma on human renal cell carcinoma heterotransplanted in nude mice]. Using human renal cell carcinoma heterotransplanted in nude mice (JRC 11: anaplastic and alveolar pattern, grade IV), the in vivo anti-tumour efficacy of tumour necrosis factor (rHu-TNF-alpha: PT-050) and IFN-alpha (nHu-IFN-alpha: HLBI), IFN-gamma (nHu-IFN-gamma: OH-6000) were investigated. The dose of TNF was 1,000, 3,000, 10,000 J.R.U. (i.p., every day), that of IFN-alpha was 1 x 10(4) and 1 x 10(5) I. U. (s.c., every day) and that of IFN-gamma was 1 x 10(4) and 1 x 10(5) I.U. (s.c., every day). Mono-therapy of TNF, IFN-alpha and IFN-gamma was not effective with regard to tumour regression rates, histological degeneration rates and survival time of the host mice. Combination therapy of TNF and IFN-alpha, IFN-gamma were also not effective with regard to tumour regression rates, but when considering histological change, sporadic disappearance of endothelium of intra-tumoural vasculature, flow of tumour cells clustered in intra-vascular cavity, and extra-vascular bleeding were observed. With special reference to survival of host mice, prominent prolongation of survival time in combination treatment, especially in TNF combination therapy groups with the dosage of 10,000 J.R.U. was observed. Therefore we concluded that there is no synergistic reaction in combination therapy of TNF and IFN against JRC 11 tumour. But combined activity of TNF and IFN on the vasculature of renal cell carcinoma (JRC 11) and the suppression of cachexia related condition were detected.

Phospholipid and lipopolysaccharide in Proteus mirabilis and its stable protoplast L-form. Difference in content and fatty acid composition. Cells of the stable protoplast L-form of Proteus mirabilis contain 1.5 to 2 times more extractable lipid, mostly phospholipid, per dry weight than cells of the bacterial form. Under identical conditions of cultivation the qualitative and quantitiative composition of the phospholipid is very similar in both cell forms. The range of mole percentages of individual phospholipid species is 78-80 for phosphatidylethanolamine, 10-13 for phosphatidylglycerol, 3.9-5.5 for diphosphatidylglycerol and 1.0-2.1 for lysophospholipid. However, all phospholipid species in the L-form differ from those of the bacterial form by a lower content of long-chain fatty acids and a higher content of short-chain fatty acids. Growth of the L-form in the presence of growth-stimulating horse serum results in a change of phospholipid composition accompanied by the uptake of phospholipid and fatty acids from the serum into L-form phospholipid. L-form protoplasts synthesize the same two types of lipopolysaccharide, I and II, that were previously identified in the bacterial form of Proteus mirabilis. However, only small amounts of the more hydrophilic lipopolysaccharide II are present in the L-form. Lipopolysaccharides from both cell forms have virtually identical polysaccharide compositions but differ strikingly in the relative content of fatty acids in their lipid-A moieties. Molar ratios of tetradecanoic acid, hexadeconoic acid and 3-hydroxytetradecanoic acid are 5:1:6 in the bacterial form and 5:0:1:6 in the L-form grown in serum-free medium. The observated differences between the bacterial form and the protoplast L-form are interpreted as results of the adaptation of the L-form to life in the state lacking an envelope by formation of a physically more stable but still sufficiently fluid protoplast membrane. A rapid method based on fatty acid analysis for the simultaneous quantitative determination of phospholipid and lipopolysaccharide content of whole cells is reported.

The structure of carbohydrate chains of blood-group substance. Isolation and elucidation of the structure of higher oligosaccharides from blood-group substance H. Twenty individual higher reduced oligosaccharides, having from seven to eleven monosaccharide units, were isolated after sodium borohydride degradation of blood-group substance H from pig stomach linings. Anion-exchange high-pressure liquid chromatography appears to be a very convenient and effective method for this kind of higher oligosaccharide mixtures separation. The oligosaccharide structures were determined by means of periodate oxidation, methylation analysis, partial acid and enzymic hydrolysis. It has been found that all the oligosaccharides investigated can be divided into four series. The oligosaccharides belonging to each series have the common oligosaccharide fragment to which terminal L-fucose and/or N-acetyl-D-glucosamine residues are attached. Comparison of all the oligosaccharide structures, including tri, penta and hexasaccharides described earlier, shows that the lower oligosaccharides represent the structural element of the higher oligosaccharides.

Expression of c-fos, c-jun and jun B in peripheral blood lymphocytes from young and elderly adults. The expression of c-fos, c-jun and jun B proto-oncogenes was studied in phytohemagglutinin (PHA) activated peripheral blood lymphocytes (PBL) from young and aged humans. Specific mRNAs for c-fos and c-jun were detectable within 30 min after cell activation and reached maximal levels within 2 h. Both c-fos and jun B mRNAs decreased to pre-activation levels within 6 h, while c-jun mRNA remained elevated. In PHA-activated PBL, no age-related differences were observed in c-fos or jun B mRNA expression. However, c-jun mRNA levels decreased significantly (1.73 +/- 0.08 vs. 1.16 +/- 0.09 arbitrary units, P < 0.01, young vs. old) in PBL from elderly individuals activated with PHA. Because previous work has demonstrated that T cells from elderly individuals may display normal proliferative responses when activated via the anti-CD2 pathway, c-jun and jun B mRNA expression was also studied in anti-CD2-activated purified T cells. No age-related differences were found in the expression of either of these two proto-oncogenes by anti-CD2 activated T cells. These results suggest that the decreased IL-2 production and proliferative response displayed by PHA-activated PBL from elderly adults may be related to age-related changes in c-jun mRNA expression and in the ratio of c-fos to c-jun mRNA.

[Treatment of immunodeficient conditions caused by viral infection with the Soviet immunomodulator kemantan in patients with pulmonary tuberculosis]. Observation of 219 patients with pulmonary tuberculosis was made to study the effect of acute respiratory viral infection (ARVI) on the course of the disease. The affected were divided into 2 groups: 136 subjects who had ARVI and 83 persons who did not have it during their stay at a hospital. Patients with infiltrative pulmonary tuberculosis, and young and middle-aged men were prevalent in both groups. It was found that ARVI promoted the aggravation of a specific process in the lungs in 19.1 per cent of the patients. Keeping in mind a large proportion of aggravations and low immunologic indices as a consequence of ARVI, 14 patients were put on kemantan. Study of the immune status of the patients who had ARVI and received kemantan demonstrated a significant increase in the formation of blasts and the concentration of T cells whose functional activity tended to rise. At the same time the above-mentioned indices remained intact or tended to drop in patients receiving no kemantan. The Soviet immunomodulator kemantan is recommended for a combined treatment of the pulmonary tuberculosis patients who had intercurrent viral infection to stimulate cellular immune defences and prevent an aggravation of the specific process.

The influence of in-vitro development upon post-thaw survival and implantation of cryopreserved human blastocysts. Blastocysts from 198 patients were frozen using glycerol as cryoprotectant. No difference in the post-thaw survival of blastocysts or implantation rates was found between 177 patients (122 transfers) with all surplus embryos cultured to blastocysts before freezing and 20 patients (12 transfers) whose embryos were considered unsuitable for freezing during cleavage and were then frozen as blastocysts. Nineteen pregnancies were achieved, of which six aborted. Pre-freezing morphology was similar in blastocysts of patients in groups 1 and 2 and did not relate to their survival after cryopreservation. A significantly lower proportion with suspected damage after thawing was present among patients becoming pregnant after transfers of single blastocysts (P less than 0.01) and implanting embryos were in general more expanded at the time of transfer. No differences were detected between blastocysts resulting in normal development and those leading to abortion. The developmental consequences of damage to human blastocysts are discussed.

Diazepam and intubation in emergency treatment of seizures in children. This study was undertaken to determine the incidence of endotracheal intubation after the use of diazepam compared with phenobarbital or phenytoin in emergency treatment of seizures in children. The records of all children (98) were reviewed in a case-control fashion. A logistic regression model was used to determine whether there was an association between diazepam administration and intubation, adjusting for all other covariates (age, weight, convulsion time before first anticonvulsant was given, response latency, diagnosis, and therapy). All children were treated in an emergency department and then transported to a tertiary pediatric center by a pediatric transport team. All patients were children, with a median age of 2.7 years (range 0.17 to 15.3 years). None. Only the use of diazepam was found to be significantly associated with intubation after adjusting for all other covariates (adjusted odds ratio, 49.4; P less than .001). In the comparison of diazepam versus phenobarbital or phenytoin used as the first anticonvulsant, median response latency did not differ (27.0 vs 32.5 minutes, P greater than .83). A significant association was found between diazepam use and intubation. Response latency was not shorter when diazepam was used as the initial anticonvulsant compared with phenobarbital or phenytoin.

Dehydroepiandrosterone sulfate (DS) levels, a rapid test for abnormal adrenal androgen secretion. Dehydroepiandrosterone sulfate (DS) concentration was measured in the sera of premature and full-term infants and in children throughout puberty. Panhypopituitary, Addisonian, and virilized children were also studied. DS decreased slowly during the first weeks of life from a high level in neonates to the low levels observed between one to five years. After five years of age, DS concentration started to rise. A steeper increase was observed with the onset of puberty, and adult DS concentrations were reached in late puberty. There was no sex difference in DS concentration at any pubertal stage or bone age. Day-to-day variations were small in childhood and during puberty, but were considerable in premature infants. DS concentrations measured at 0900 h were not significantly different from those at 1700 h. There was a positive correlation of serum DS concentrations with the excretion of urinary 17-ketosteroids in boys and girls (r=0.789). Premature infants had DS concentration in or above the late pubertal range. Five panhypopituitary patients and five Addisonian patients had DS concentrations below normal. DS was markedly elevated in patients with congenital adrenal hyperplasia and in one girl with adrenal carcinoma, and was suppressible with dexamethasone in the former. The ease of measurement and the small amount of blood required make serum DS determination a useful guide for adrenal androgen secretion.

The effects of intraocular pressure elevation on optic nerve axonal transport in the monkey. Blockage of axonal transport by intraocular pressure (IOP) elevation was studied quantitatively in monkey eyes, using liquid scintillation counting. After 5 h of IOP elevation (perfusion pressure of 30 mmHg), axonally transported protein was measured in the distal third of each optic nerve, which was divided into superotemporal, inferotemporal, superonasal, and inferonasal portions. The ratio of the amount of radioactive protein in each portion of the optic nerve to that in the whole optic nerve was calculated. In eyes with IOP elevation, the mean ratio for the temporal optic nerve was significantly lower than that for the nasal optic nerve. It appeared that axonal transport was not affected homogenously throughout the optic nerve but was more impaired by the temporal half of the optic nerve following IOP elevation.

MR imaging of brain maturation in normal and developmentally handicapped children. White matter myelination was assessed in the frontal, temporal, and occipital lobes and in the internal capsule in 91 neurodevelopmentally handicapped infants on T2-weighted images (spin echo 3,000/120 ms) and compared with myelination scores from 53 normal control subjects. Clinical diagnosis was birth asphyxia (34), seizures with delays of various causes (33), congenital infections (15), and intracerebral hemorrhages (9). Myelination in the total group of patients was generally delayed. However, we found distinct differences in myelin deposition between groups. Myelination of handicapped children with seizures or with intrauterine infections was retarded most severely at all ages. Children with intracerebral hemorrhages were almost never significantly different from normals in any part of the brain, whereas children with birth asphyxia had myelination scores in between. We conclude that magnetic resonance staging of developmental processes, such as myelination, in the infants' brain helps to recognize delays at an early age.

Congenital Pelizaeus-Merzbacher disease (Seitelberger type), malformation and cystic degeneration of the central nervous system. The present paper reports on the case of a neonate child with multiple malformations affecting osteogenesis and the central nervous system (microcephaly, pachygyria). Morphologically, myelin staining supplied evidence of the total lack of myelin sheaths (myelin aplasia). The cerebellar cortex was malformed and altered by cystic degeneration. Electron microscopy confirmed the aplasia of the myelin sheaths and revealed the presence of concentric multilamellar formations in the glial cells (myelination glia), and in areas of cystic degeneration. The morphologic aspects clearly showed the relationship of this congenital aplasia of the myelin sheaths with the congenital Pelizaeus-Merzbacher disease (Seitelberger type). The cystic degeneration differs from the spongy degeneration of the brain (van Bogaert-Bertrand disease) and should be considered a result of maldeveloped nervous tissue.

The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation. To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.

Activation of the alternative (properdin) pathway of complement by Candida albicans and related species. Accumulations of neutrophilic granulocytes within the epidermis and beneath the stratum corneum of the skin are a prominent histologic feature of experimental and clinical candidiasis. The mechanism of cell accumulation was studied by standard chemotactic methods. Suspensions of viable or heat-killed Candida sp caused marked chemotaxis of human neutrophils in fresh serum. Culture supernatants of Candida sp were not chemotactic. Chemotaxis was dependent upon fresh serum, and could be abolished by heating the serum to 56 degress C for 30 min, suggesting that interaction of these organisms with a heat-labile serum factor generated a chemoattractant. Incubation of Candida sp with fresh human serum resulted in the conversion of the third component of complement and properdin factor B, as measured by immunoelectrophoresis. Conversion did not occur in serum chelated with EDTA, or heated to 50 degress C for 30 min (to destroy factor B). Conversion was present in serum chelated with EGTA (to deplete calcium), or genetically deficient in the fourth component of complement. By contrast, the three components of the kinin-forming system (Hageman factor, prekallikrein, high-molecular-weight kininogen) were not activated by Candida sp. We suggest that Candida sp do not release a chemotactic substance but, in the presence of serum, activate the alternative pathway of complement, generating chemotactic factors.

Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation. Twelve of 178 (7%) liver transplant patients underwent endoscopic retrograde cholangiopancreatography (ERCP) after transplantation. The indications for ERCP were persistent or late onset cholestasis, recurrent cholangitis, and suspected biliary leaks or strictures. The time between transplantation and ERCP ranged from 44 to 330 days (median 153 days). Biliary complications diagnosed by ERCP included biliary sludge in the form of casts, calculi, or debris (n = 7); bile leaks (n = 2); a biliary stricture (n = 1), and complete biliary obstruction (n = 1). One patient had a normal cholangiogram after transplantation. Biliary sludge was detected by ultrasound before ERCP in only one of six patients. Eight patients underwent endoscopic papillotomy, followed by clearance of biliary sludge in four and dilatation of a biliary stricture in one. Two patients bled after papillotomy but neither required surgical intervention. At a median follow up of 1.2 years (range 0.5-2.8 years), nine patients are well and three have died. ERCP provides both accurate diagnosis of biliary complications after liver transplantation and treatment that obviates the need for additional surgery in selected patients.

Screening methods for assessment of biodegradability of chemicals in seawater--results from a ring test. An international ring test involving 14 laboratories was organized on behalf of the Commission of the European Economic Communities (EEC) with the purpose of evaluating two proposed screening methods for assessment of biodegradability in seawater: (a) a shake flask die-away test based primarily on analysis of dissolved organic carbon and (b) a closed bottle test based on determination of dissolved oxygen. Both tests are performed with nutrient-enriched natural seawater as the test medium and with no inoculum added other than the natural seawater microflora. The test methods are seawater versions of the modified OECD screening test and the closed bottle test, respectively, adopted by the Organization for Economic Cooperation and Development (OECD) and by the EEC as tests for "ready biodegradability." The following five chemicals were examined: sodium benzoate, aniline, diethylene glycol, pentaerythritol, and 4-nitrophenol. Sodium benzoate and aniline, which are known to be generally readily biodegradable consistently degraded in practically all tests, thus demonstrating the technical feasibility of the methods. Like in previous ring tests with freshwater screening methods variable results were obtained with the other three compounds, which is believed primarily to be due to site-specific differences between the microflora of the different seawater samples used and to some extent also to differences in the applied concentrations of test material. A positive result with the screening methods indicates that the test substance will most likely degrade relatively rapidly in seawater from the site of collection, while a negative test result does not preclude biodegradability under environmental conditions where the concentrations of chemicals are much lower than the concentrations applied for analytical reasons in screening tests. Nevertheless, the screening tests are considered useful and cost-effective tools for an initial assessment of biodegradability in marine environments.

Comparison of exit-site infections in disconnect versus nondisconnect systems for peritoneal dialysis. To determine if disconnect systems reduce the incidence of exit-site infections when compared to nondisconnect systems. We prospectively monitored exit-site infections and peritonitis rates in 96 disconnect patients (Y-set, automated peritoneal dialysis (APD)) and 60 nondisconnect patients (spike, ultraviolet connection device (UVXD)). A freestanding chronic peritoneal dialysis unit staffed by physicians from both a medical school and a private setting. All patients who began peritoneal dialysis at our unit were monitored, regardless of cause of end-stage renal disease (ESRD) or age. Patients were dialyzed using the system (Y-set, spike, etc.) most appropriate for their life-style and their ability to administer self-care. We attempted to follow disconnect and nondisconnect patients for a similar median time on dialysis and compared differences in exit-site infections. Peritonitis rates (episodes/pt year) were reduced for disconnect (0.60) versus nondisconnect (0.99) systems (p = 0.0006). Despite the marked reduction in peritonitis rates, there was no difference in exit-site infection rates (0.35 vs 0.38), the time to the first exit-site infection, or the time to the first catheter removal for disconnect versus nondisconnect groups. When individual systems were compared, differences in exit-site infection rates (episodes/pt years) were noted (0.62,spike; 0.26,UVXD; 0.32,Y-set; 0.41,APD). We found no overall difference in exit-site infection rates for disconnect versus nondisconnect systems, despite a reduction in peritonitis rates for disconnect systems.

A radical approach to bacterial panniculitis of the abdominal wall in the morbidly obese. The morbidly obese patient, although at risk for many perioperative complications of radical surgery, paradoxically presents the opportunity for wide excision of abdominal soft-tissue infections. This report describes the successful radical surgical management of bacterial panniculitis of the abdominal wall occasioned by a variety of extrafascial and intraperitoneal sources in 13 patients. All patients were followed up for a minimum of 2 years, except for one patient who died 2 months after hospital discharge. The remainder are alive with intact fascial closure and no pannicular infection. A radical approach to the infected abdominal wall, incorporating wide en-bloc excision of skin, subcutaneous tissue, muscle, and strangulated intestine, facilitates successful fascial and skin closure in a noninfected field in the morbidly obese.

A case of cicatricial pemphigoid with circulating IgA and IgG antibodies directed against 280 kD, 165 kD and 120-130 kD epidermal antigens. A case of subepidermal autoimmune blistering disease in an 86-year-old woman is reported. Clinical features were those of a cicatricial pemphigoid, with prominent mucosal involvement leading to conjunctival and nasal scarring. Direct immunofluorescence findings were consistent with either cicatricial pemphigoid or linear IgA dermatosis, since both IgG and IgA linear deposits were found at the basal membrane zone. Immunoelectron microscopy of perilesional skin revealed IgA deposits within the lamina lucida and immunoblotting of the patient's serum disclosed IgA and IgG antibodies directed against epidermal antigens of 280, 165 and 120-130 kD.

Ligands for antibody to M-protein are exposed at the surface of influenza virions: effect of proteolytic treatment on their activity. Antiserum to pure M-protein extracted from PR8 virions neutralized the infectivity and inhibited the haemagglutinating activity of various influenza A virions. It agglutinated concentrated suspensions of these virions and fixed complement in their presence. Antibodies to M-protein were readily absorbed by intact virions or by spikeless particles obtained after proteolytic treatment, giving clear evidence that M-protein is exposed at the surface of the virus envelope. The data suggest that when antibodies to M-protein occupy specific ligands exposed at the surface of the virion they interfere with sites critical for infectivity and haemagglutinating activity.

Atherosclerosis and body build. In a large autopsy series the relation between various measures of body build and aortic and coronary atherosclerosis, coronary stenosis, and myocardial lesions was studied. Stature was not associated with any of these variables. Various measures of obesity all showed an association between obesity and the above-mentioned variables. Obese people were found to have more coronary atherosclerosis, coronary stenosis, and myocardial lesions than thin people, a difference that persisted, in a reduced form, when hypertensives and diabetics were excluded. When compared with the standardized average atherosclerosis group to exclude the effect of "wasting diseases", and when hypertensives and diabetics were excluded, neither the extent of atherosclerotic lesions nor the prevalence of coronary stenosis were increased in obese subjects. Obese men but not obese women, however, had more myocardial lesions, especially fresh myocardial infarction.

In vitro production of cyanide in normal human blood and the influence of thiocyanate and storage temperature. Normal human blood stored at room temperature (about 20 degrees C) may, over a period of weeks, undergo a slow transformation of its cyanide content. In contrast, when normal blood is stored at -20 degrees C there is formation of cyanide, usually occurring most rapidly during the first few days of storage. Peak concentrations are never greater than 20 microgram/100 ml, and although some fluctuation in concentration occurs over several months of storage at deep freeze temperature, levels are always higher than in the freshly drawn blood. The amount of cyanide produced appears to be a function of both the initial thiocyanate concentration and the freezing and/or thawing of blood. Blood stored at refrigerator temperature (about 4 degrees C) has the least fluctuation in cyanide concentration over a storage period up to three months. During this study it was found that there is significant difference in whole blood cyanide concentration between smokers and nonsmokers.

The location and nucleotide sequence of the thymidine kinase gene of bovine herpesvirus type 1.2. On the basis of their restriction endonuclease digestion patterns, four Australian bovine herpesvirus type 1 (BHV-1) isolates were classified as belonging to the BHV-1.2a subtypes. The thymidine kinase (TK) genes of all four BHV-1.2a isolates were located on a 3.5 kb SalI restriction fragment. This is in contrast to North American and European BHV-1.1 isolates whose TK genes are contained on a 2.6 to 2.8 kb SalI fragment. The restriction fragments containing the TK genes were cloned into phagemid vectors and their sequences determined using the dideoxynucleotide chain termination method. The BHV-1.2a isolates possessed identical TK gene sequences, which differed from previously published TK sequences for the LA and 6660 BHV-1.1 strains. In addition to five single base alterations, there were six separate base insertions which resulted in two major frameshifts which spanned an area of 72 amino acids or 20% of the expressed TK gene product. The predicted amino acid sequence exhibited a higher degree of similarity to other herpesvirus TKs, suggesting that previously published TK gene sequences may have been incorrect. The present nucleotide sequence and corresponding amino acid composition reinforces previous observations concerning regions of herpesvirus TK amino acid conservation and should assist in future studies into the evolution and functional domains of herpesvirus TKs.

Characterization of the enhancer region for germline transcription of the gamma 3 constant region gene of human immunoglobulin. A constant region gene (C) of the immunoglobulin heavy chain can be transcribed as germline transcripts from a promoter located upstream of a switch region. We have studied the structure and function of the human C gamma 3 promoter region. When the human IgM-producing cell line SSK41 is stimulated with interleukin 4 (IL-4) in the presence of phorbol myristate acetate (PMA) or Staphylococcus aureus Cowan I, expression of germline C gamma 3 transcripts was specifically augmented within 4 h. Upstream DNA fragments flanking the I gamma 3 exon were fused with a reporter gene and tested for IL-4-induced promoter/enhancer activity by transfection of SSK41 cells. The DNA fragment between 450 and 250 bp upstream of the transcription initiation site of the C gamma 3 gene was shown to be required for transcriptional up-regulation by PMA and IL-4. The upstream 514 bp fragment of the I gamma 3 flanking region was shown to contain an enhancer activity in response to PMA and IL-4.

Regulation of corticotropin-releasing factor mRNA in neuroendocrine and autonomic neurons by osmotic stimulation and volume loading. Corticotropin-releasing factor (CRF) has been reported to be expressed in oxytocin-containing magnocellular neurosecretory neurons of the paraventricular (PVN) and supraoptic (SON) nuclei, and in Barrington's nucleus, a pontine micturition center. Each of these cell groups is known to play a role in fluid and electrolyte homeostasis. To gain a better understanding of the role of CRF in this context, the effects of osmotic stimulation and volume loading on CRF mRNA levels in the PVN, SON and Barrington's nucleus were examined using in situ hybridization histochemistry with an 35S-labeled cRNA probe. Adult male rats received either normal tap water (control), or hypertonic (2%) saline (HS) for up to 3 days. In a second experiment, normal saline was infused through a jugular vein cannula at 6 ml/h for 3 days; control rats were cannulated but received no infusion. Relative levels of CRF mRNA were compared by estimating both the number of positively hybridized cells and the density of silver grains in emulsion-dipped autoradiograms. HS treatment resulted in marked increases in CRF mRNA in the magnocellular neurosecretory system. All recognized oxytocinergic cell clusters, i.e., the anterior, medial and posterior magnocellural subdivisions of the PVN, the dorsal aspect of the SON, and components of the accessory magnocellular system, displayed this effect. By contrast, HS treatment resulted in significant decreases in CRF mRNA levels in the parvocellular (hypophysiotropic) division of the PVN and in Barrington's nucleus. By contrast, volume loading, which failed to affect plasma osmolality, significantly increased CRF mRNA levels in Barrington's nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Application of multilocus enzyme electrophoresis to epidemiologic investigations of Xanthomonas maltophilia. To test the utility of a newly developed multilocus enzyme electrophoresis typing method for Xanthomonas maltophilia. Isolates were first screened by slide agglutination, which served as the standard to characterize the outbreak strains. All isolates were then subjected to multilocus enzyme electrophoresis and the results analyzed based on epidemiological data. This outbreak occurred in a shock-trauma intensive care unit of a large general community hospital. Patients admitted to the shock-trauma intensive care unit who had X maltophilia isolated from any site greater than or equal to 24 hours after admission met the case definition. Specimens from patients who fit the case definition were characterized, as were specimens from other patients that were used as controls for nonoutbreak isolates. Environmental samples were also evaluated for X maltophilia. Most of the 64 isolates received during this outbreak were serotype 10, and when they were subjected to multilocus enzyme electrophoresis, one electrophoretic type predominated and correlated to most outbreak isolates. Unrelated isolates of serotype 10 from other institutions all exhibited unique electrophoretic types. Application of multilocus enzyme electrophoresis to X maltophilia outbreaks is a valuable addition to the characterization of suspected outbreak strains.

Pharmacokinetics of amikacin in patients with impaired renal function. Pharmacokinetic parameters were determined after a single intramuscular injection of 7.5 mg of amikacin/kg to 10 volunteers with impaired renal function (creatinine clearance rate, 2.2-65ml/min per 1.73 m2) and to six volunteers with normal renal function. The mean peak concentrations of amikacin in sera of the two groups did not differ significantly from each other and exceeded by two to five times the reported in vitro minimal inhibitory concentrations for the majority of Pseudomonas aeruginosa and Enterobacteriaceae strains. There was a significant linear relation between the elimination rate constant of amikacin and the rate of creatinine clearance; there was a significant nonlinear relation between the half-life of amikacin and the serum creatinine concentration. Knowledge of these relations may aid in adjustment of the dosage of amikacin in patients with impaired renal function, especially when such information is used in conjunction with serum assays of amikacin.

Treatment of breast cancer in two teaching hospitals: a comparison with consensus guidelines. We compared the initial treatment of 383 patients with breast cancer in two central London teaching hospitals during 1986 with the guidelines of the King's Fund Consensus Conference for breast cancer treatment held in London the same year. The majority of patients (68%) received lumpectomy and 18% received mastectomy. Lumpectomy was followed by radiotherapy for 95% of cases but 30% of mastectomy patients also received radiotherapy. Only 42% of the patients had surgical sampling of the axillary nodes. Cytotoxic chemotherapy was recorded for 27% women under 50, but also for 16% women age 50 or more. Tamoxifen was given to 58% of women aged 50 or more, but also to 26% of women under 50. We conclude that there are discrepancies between consensus guidelines and clinical practice. Further study is needed to determine whether these variations are clinically important, and whether similar variations exist elsewhere in Europe.

Molecular cloning of the 130-kilodalton mosquitocidal delta-endotoxin gene of Bacillus thuringiensis subsp. israelensis in Bacillus sphaericus. A 3.7-kilobase (kb) XbaI fragment harboring the cryIVB gene (L. Thorne, F. Garduno, T. Thompson, D. Decker, M. A. Zounes, M. Wild, A. M. Walfield, and T. J. Pollock, J. Bacteriol. 166:801-811, 1986) which encoded a 130-kilodalton (kDa) mosquitocidal toxin from a 110-kb plasmid of Bacillus thuringiensis subsp. israelensis 4Q2-72 was cloned into pUC12 and transformed into Escherichia coli. The clone with a recombinant plasmid (designated pBT8) was toxic to Aedes aegypti larvae. The fragment (3.7 kb) was ligated into pBC16 (tetracycline resistant [Tcr]) and transformed by the method of protoplast transformation into Bacillus sphaericus 1593 and 2362, which were highly toxic to Anopheles and Culex mosquito larvae but less toxic to Aedes larvae. After cell regeneration on regeneration medium, the Tcr plasmids from transformants (pBTC1) of both strains of B. sphaericus were prepared and analyzed. The 3.7-kb XbaI fragment from the B. thuringiensis subsp. israelensis plasmid was shown to be present by agarose gel electrophoresis and Southern blot hybridization. In addition, B. sphaericus transformants produced a 130-kDa mosquitocidal toxin which was detected by Western (immuno-) blot analysis with antibody prepared against B. thuringiensis subsp. israelensis 130-kDa mosquitocidal toxin. The 50% lethal concentrations of the transformants of strains 1593 and 2362 against A. aegypti larvae were 2.7 X 10(2) and 5.7 X 10(2) cells per ml, respectively. This level of toxicity was comparable to the 50% lethal concentration of B. thuringiensis subsp. israelensis but much higher than that of B. sphaericus 1593 and 2362 (4.7 X 10(4) cells per ml) against A. aegypti larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

The sharpening of cochlear frequency selectivity in the normal and abnormal cochlea. In the normal (anaesthetized) animal cochlea, the frequency threshold curves for single primary fibres are up to an order of magnitude sharper than the analogous function derived from various reported measurements of the basilar membrane amplitude of vibration. This enhanced neural frequency selectivity is found in the same species and under conditions similar to those in which the mechanical measurements are taken. The sharpening process (at least near threshold) appears to be linear and is not dependent upon lateral inhibitory mechanisms. The variability of the neural frequency selectivity and its vulnerability to metabolic, chemical and pathological influences suggests the hypothesis that the sharpening is due to some form of "second filter" subsequent to the relatively broadly tuned basilar membrane. All fibres recorded from in the cochlear nerve in the normal cochlea show this enhanced frequency selectivity; in contrast, in pathological cochleas, all fibres, or a substantial proportion, have high-threshold, broadly tuned characteristics, approximating to those of the basilar membrane. The frequency selectivity of normal cochlear fibres is adequate to account for the analogous psychophysical measures of hearing. It is proposed that loss of this normal frequency selectivity occurs in deafness of cochlear origin, accounting for widening of the critical band. A new hypothesis for recruitment is proposed on this basis.

Expression of a multidrug-resistance gene in human malignant lymphoma and related disorders. The expression of mdr1 gene was measured to determine whether it plays a role in clinical resistance to chemotherapy of human malignant lymphomas. mdr1 expression was found in 4 of 9 cases resistant to chemotherapy. Expression of mdr1 was not detectable in any of 7 chemotherapy-sensitive tumors. The 2 cases of reactive lymphadenitis and the 3 samples of normal mononuclear cells did not show any expression of mdr1 gene, either. These results indicate that expression of the mdr1 gene is not always detectable in cases of malignant lymphoma resistant to chemotherapy, but the detectable expression of mdr1 gene may predict clinical resistance to chemotherapy.

Anaerobic growth of Escherichia coli on formate by reduction of nitrate, fumarate, and trimethylamine N-oxide. Anaerobic growth of E. coli, strain K-10, depending on formate oxidation by nitrate, fumarate, and trimethylamine N-oxide was followed in a medium containing peptone. The presence of formate and peptone was indispensable for growth with fumarate and trimethylamine N-oxide reduction. While there was no growth in the absence of acceptor, growth was observed in the absence of formate by nitrate reduction though not as much as under aerobic conditions. Per mole consumed formate equimolar succinate or trimethylamine was formed, but 1.2 mole of nitrate was produced, probably depending partly on peptone oxidation. The molar growth yield on formate was found to be 6.5, 7.6, and 7.0 g cells/mole depending on the reduction of nitrate, fumarate, and trimethylamine N-oxide, respectively, suggesting the formation of one mole ATP coupled to the anaerobic electron transfers from formate.

Investigation of biological activity of antigen--immunosuppressive drugs conjugates. The influence of conjugate 6MP with bovine gamma-globulin on some cellular immunologic reactions was investigated. The animals were immunized with the protein carrier and then conjugate or its components, in not coupled form, were introduced. Selective, but not strong, suppression of the immunological answer was observed in the migration inhibition of the mice splenocytes and the foot pad test. Conjugate was not changing the activity of the factor increasing vascular permeability. It was also confirmed, that conjugates of the nonsteroidal antiinflammatory drugs, except for conjugate of phenylbutazone with HSA, were not different in its influence (in the hyperaemic and oedema tests) from the individual components in not coupled form.

Suppressor cell function in oral lichen planus. Oral lichen planus (OLP) is a common inflammatory condition of the oral mucous membranes which affects between one and two percent of the general population. In accordance with the protracted clinical course of OLP and its association with known auto-immune diseases, the level of self-tolerance is questionable and possibly diminished in patients with this disorder. Normal suppressor T lymphocyte function is reputedly an essential element in the maintenance of self-tolerance, and deficient cell-mediated suppressor activity is implicated in the pathogenesis of auto-immune diseases. For assessment of in vitro cell-mediated suppressor activity in OLP, peripheral blood mononuclear cells (PBMC) from ten patients with OLP and from 11 control subjects were activated with the plant mitogen concanavalin A (Con A), followed by co-culture with autologous responder cells. The ability of irradiated Con A-activated cells to suppress the proliferation of Con A-stimulated responder cells was determined. Con A-induced suppressor activity of PBMC in the OLP patients was significantly less than that in control subjects (p = 0.001). Results of the present investigation complement previous in vitro findings which provided indirect evidence of deficient cell-mediated suppressor activity in OLP, particularly a decreased proportion of circulating CD4+CD45RA+ lymphocytes and reduced Con A-stimulated PBMC proliferation. The depressed Con A-induced suppressor activity of PBMC in the OLP patients provides direct evidence of deficient in vitro cell-mediated suppressor function in OLP, and suggests that defective cell-mediated suppressor circuits and reduced self-tolerance may be involved in the pathogenesis of this disorder.

[Experimental pulmonary edema: pathophysiological mechanism (author's transl)]. Traumaticed tissue or organs show different reactions to oral and parenteral application of watery solutions. Tissue traumaticed or not does incline to edema. 2. In its central position in blood circulation, its capability of water storage and distribution as well in its regulatory function of the cardiac output, the lung is very suitable for transportation of fluid. 3. If physiologic transportation exceeds a maximum (renal and cardiac insufficiency, high temperature, infusion) and if lymphatics are blocked, edema results in the interstitial and intraalveolare space. 4. Fatal edema is prevented during the first 48 h by applicating proteinase inhibitor drug; Trasylol immediatly after trauma. 5. Edema is significantly diminished applicating Benzopyrone (Venalot), as proven biochemically and electromicroscopically. 6. Taking the findings, it is necessary to considerate a new concept of fluid therapy.

Perinatally acquired neonatal tuberculosis: report of two cases. Perinatally acquired neonatal tuberculosis occurs rarely, is difficult to diagnose, may be the indicator of untreated tuberculosis in the mother, and could result in nosocomial transmission to neonatal patients, visitors to neonatal intensive care units, and health care workers. The disease may be more common in certain ethnic and social groups. Neonatal mortality approaches 30%. We report two cases with different outcomes. A neonate was treated for clinical miliary tuberculosis and survived; Mycobacterium tuberculosis was cultured from bronchoscopic washings, maternal genital fluids, and tissues. A second infant died at age 46 days, and autopsy disclosed miliary tuberculosis of lungs, mediastinal and mesenteric nodes, liver, spleen, and bone marrow. The lungs were most severely affected, but the placenta and central nervous system were not involved. The histopathology was not granulomatous. After the diagnosis in the infant, the mother was ascertained to have pulmonary and genital tuberculosis. Fetal and neonatal tuberculosis could be acquired transplacentally as prenatal tuberculous chorioamnionitis, perinatally through aspiration and ingestion of infected maternal genital tissues and fluid, or postnatally through droplet spread from cases of active tuberculosis. These two neonates probably acquired the disease perinatally from maternal genital tuberculosis.

Quantitative characterization of beta-adrenergic receptor subtypes in porcine adipocytes. 1. Two populations of beta-adrenergic receptor (beta AR) subtypes and their proportions were characterized in adipocytes isolated from subcutaneous adipose tissue of castrated male crossbred pigs (60-85 kg). 2. Specific binding of the radioligand 125I-iodopindolol (IPIN) to crude plasma membranes (70-90% of total binding) reached equilibrium conditions in 30 min (38 degrees C), was tissue concentration-dependent, stereospecific and saturable (bmax = 168 +/- 5.8 fmol/mg protein). 3. Displacement curves by ICI 89,406 were best-fit by a two site model (P less than 0.01) that indicated the presence of two receptor populations and selectivity of IPIN for the beta 2AR subtype. 4. Forty-five percent of the receptors had a high affinity for ICI 89,406, Ki = 2.27 +/- 0.68 nM and were classified as beta 1AR.

Preventive effects of inhaled formoterol and salbutamol on histamine-induced bronchoconstriction--a placebo-controlled study. The preventive effects of inhaled formoterol (a new beta 2-agonist) and salbutamol aerosols on histamine-induced bronchoconstriction were studied in 12 patients with mild or moderate asthma in a placebo-controlled, double-blind study. Three hours after the administration of 12 micrograms formoterol, 200 micrograms salbutamol (doses with equal bronchodilator effects) or placebo via aerosol, histamine challenge was undertaken, using a dosimetric jet nebulizer with controlled tidal breathing. The noncumulative dose of histamine diphosphate aerosol provoking a 15% fall in FEV1 (PD15) was calculated. The PD15 after inhalation of 12 micrograms formoterol was significantly higher than that after 200 micrograms salbutamol (median values 640 and 310 micrograms, respectively; p < 0.01). For both treatments, the PD15 was significantly higher than that after placebo (median 185 micrograms). The results indicate that the preventive effect against histamine-induced bronchoconstriction at 3 h after drug is significantly better with formoterol than with salbutamol when using inhaled doses with an equal acute bronchodilator effect.

[Evaluation of vaccine coverage in children under two years of age in Kinshasa (Zaire)]. Despite efforts to make immunization against preventable diseases available to all children in Zaire, only about 33% of the children living at Kinshasa were immunized in 1986. The compliance with the vaccination schedules was evaluated in 211 children less than 2 years of age consulting in the largest medical center of Kinshasa during one week in September 1989. Socio-demographic data on the parents and histories of infectious preventable diseases in children were also collected. 93% of the children were immunized against tuberculosis, 85% against diphtheria, tetanus, pertussis and poliomyelitis, 76% against measles. Compliance with the vaccination schedule was higher when the mothers were better educated, or when they worked in the public service. 25% of the children had not been immunized against measles at the age of 9 months. The vaccine schedule and the strategy must still be improved.

The separation of the mycobactins from Mycobacterium smegmatis by using high-pressure liquid chromatography. The family of mycobactins from Mycobacterium smegmatis were resolved into seven fractions by high-pressure liquid chromatography. This separation was by virtue of the differences in length and character of the long acyl substituents as shown by g.l.c. of the methyl esters of the isolated fatty acids from the fractions. As t.l.c. could also resolve the individual mycobactin fractions, it too must rely on the same differences to effect separation. As the lengths of the acyl chains were modulated by the growth conditions, a specific range of acyl groups may not be needed for mycobactin to function. This technique provides a simple means of rapidly characterizing crude mycobactins from all mycobacteria.

Yeast bezoar formation following gastric surgery. Yeast bezoar seems to be a relatively common late complication after various gastric operations. The incidence of bezoar depends decisively on the nature of the operation. Vagotomy in particular is conducive to the formation of a bezoar. Vagotomy + Billroth I resection proveded the most propitious conditions for the growth of yeast, for every one-half of the patients in this group developed a bezoar. Yeast bezoars usually appear within a year of the operation. The majority disappear during the first follow-up year, many without any therapy. However, in some cases the bezoar was a rather inconvenient late complication of gastric surgery and one that gave symptoms. It is difficult to draw any definite conclusions concerning the effect of therapy on the disappearance of the bezoar. We used gastric lavage and antimycotics as well as substances that increase gastric acidity. There is still no known method of preventing the formation of yeast bezoars. In the present consensus, a change in the acid conditions and disturbed gastric motility postoperatively are conducive to the formation of a bezoar.